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Toxins 2019, 11(3), 176; https://doi.org/10.3390/toxins11030176

Review
Harmful Effects and Control Strategies of Aflatoxin B1 Produced by Aspergillus flavus and Aspergillus parasiticus Strains on Poultry: Review
1
Key Laboratory of Animal Nutrition and Feed Science (South China) of Ministry of Agriculture, State Key Laboratory of Livestock and Poultry Breeding, Guangdong Public Laboratory of Animal Breeding and Nutrition, Guangdong Key Laboratory of Animal Breeding and Nutrition, Institute of Animal Science, Guangdong Academy of Agricultural Sciences, Guangzhou 510640, China
2
Department of Animal Production, Faculty of Agriculture, Cairo University, Giza 12613, Egypt
*
Author to whom correspondence should be addressed.
Received: 7 March 2019 / Accepted: 20 March 2019 / Published: 23 March 2019

Abstract

:
The presence of aflatoxin B1 (AFB1) in poultry diets decreases the hatchability, hatchling weight, growth rate, meat and egg production, meat and egg quality, vaccination efficiency, as well as impairing the feed conversion ratio and increasing the susceptibility of birds to disease and mortality. AFB1 is transferred from poultry feed to eggs, meat, and other edible parts, representing a threat to the health of consumers because AFB1 is carcinogenic and implicated in human liver cancer. This review considers how AFB1 produced by Aspergillus flavus and Aspergillus parasiticus strains can affect the immune system, antioxidant defense system, digestive system, and reproductive system in poultry, as well as its effects on productivity and reproductive performance. Nutritional factors can offset the effects of AFB1 in poultry and, thus, it is necessary to identify and select suitable additives to address the problems caused by AFB1 in poultry.
Keywords:
aflatoxin B1; immunity; nutritional factor; productivity
Key Contribution: AFB1 produced by specific strains of A. flavus and A. parasiticus; even at low concentrations; can have highly deleterious impacts on poultry productivity. Nutritional factors; such as inorganic and organic AFB1 binders; as well as antioxidants; vary in terms of their efficiency and the mechanism involved when counteracting the deleterious effects of AFB1 on poultry.

1. Introduction

The allowance level for aflatoxins (AFs) is low in poultry feedstuffs compared with other mycotoxins and, thus, poultry feed is at a high risk of contamination with AFs. AFs are found in corn, which is one of the main sources of energy for poultry, as well as other feedstuffs, such as corn dried distiller’s grains with solubles, peanut meal, and cotton seed meal [1,2,3,4]. The growth of Aspergillus flavus (A. flavus) or Aspergillus parasiticus (A. parasiticus) in poultry feedstuffs is usually accompanied by the production of many toxic secondary metabolites, such as aflatoxins B1 (AFB1), B2 (AFB2), G1 (AFG1), and G2 (AFG2) [5]. Among these metabolites, AFB1 is the most dangerous and abundant mycotoxin [6,7]. The hazards from AFB1 in poultry are associated with low productivity and high susceptibility to diseases, which can have negative impacts on the poultry producer’s income as well as affecting human health [8,9,10,11]. AFB1 is recognized as being hepatotoxic, carcinogenic, and mutagenic [12]. AFB1 is the third most important cause of liver cancer, especially in sub-Saharan Africa and developing countries in Asia [13].
Eggs contain vitamins, minerals, and lipids, and are considered to be the cheapest source of animal protein [14,15], while poultry meat contains less fat and cholesterol than does ruminant meat [16,17,18]. Eggs, poultry meat, and/or products based on one or both, therefore, are consumed as part of the daily diet for many people [19,20,21,22]. Due to the harmful impacts of AFB1 on human health, the European Union has restricted the amount of AFB1 that can be present in food to 2.0 μg/kg [23]. AFB1 is transferred from poultry feed to eggs, meat, and other edible parts [24,25,26,27,28,29,30]. This review, therefore, considers the effects of AFB1 produced by A. flavus and A. parasiticus strains on poultry productivity through influencing the functionality of different organs, and examines how nutritional factors can help to address this problem.

2. Effects of Aflatoxin B1 Produced by Aspergillus flavus and Aspergillus parasiticus Strains on Poultry

2.1. Productivity

Table 1 summarizes the concentrations of AFB1 produced by A. parasiticus and A. flavus strains that detrimentally affected poultry productivity. The concentration of AFB1 that causes aflatoxicosis and impairs bird productivity depends on the fungal strain and the susceptibility of the bird species to AFB1. The susceptibility of bird species to AFB1 can be summarized as follows: aflotoxicosis occurred in breeders hens, broilers, quail, White Pekin ducks, and turkeys when they consumed diets containing 3000, 2000, 1500, 1100, and 500 μg AFB1/kg produced by A. parasiticus (NRRL 2999), respectively [31,32,33,34,35,36,37]. It has been reported [5] that the susceptibility of poultry species to AFB1 varies because each species has a different capacity for converting AFB1 to AFB1-8,9-epoxide (AFBO, the more toxic form) via the production of cytochrome P450 isozymes, which finally affect the formation and concentration of AFBO [38,39,40] and, thus, the concentrations of AFBO–DNA adducts (causing DNA lesions) [41,42]. It is unclear whether the same mechanism that explains the sensitivity of various poultry species to AFB1 can also explain the deleterious impacts of AFB1 produced by a specific fungal strain, even with a low concentrations, or if other mechanisms might be involved.

2.2. Egg and Meat Quality

The biggest problem caused by AFB1 contamination in poultry production is not the economic loss due to poor eggshell quality and the reduced yolk color score, which can be readily observed and lead to rejection by consumers, but instead it is attributable to the AFB1 toxin, which is readily transferred from the diet to products (meat, eggs, and edible parts). Clearly, this toxin cannot be visually observed and specific tests are required for its detection to assess the possible threat to human health. It has been reported [34] that egg shell thickness and eggshell proportion were affected in quail that consumed a diet containing 1500 μg AFB1/kg produced by A. parasiticus (NRRL 2999). Similarly, reductions in the eggshell thickness and yolk color score, as well as high concentrations of AFB1 in the eggs and meat (1.4 and 18.0 μg/kg, respectively), were found when laying hens were fed a diet containing 2500 μg AFB1/kg produced by A. parasiticus (SRRC 148) from 2–40 weeks of age [9]. Moreover, the addition of 500 μg AFB1/kg produced by A. parasiticus (ATCC 15517) to the diet of hens from 15–67 weeks of age led to the accumulation of 3.5 and 18.2 μg AFB1/kg eggs at the beginning of the experiment and after one year of feeding, respectively [24]. However, increasing the concentration of added AFB1 obtained from A. flavus (NRRL 6540; CECT 2687) 10-fold compared with that used by Kim et al. [24] led to a lower accumulation of AFB1 (0.446 μg/kg) in the eggs after 21 days [51]. In addition, the AFB1 residue level in breast muscles from breeder hens aged 46 weeks was 0.03 μg/kg [51] compared with 18.0 μg/kg according to Pandey and Chauhan [9]. The different results obtained in these three previous studies [9,24,51] may be explained by the use of different fungal strains to produce AFB1, the bird ages, and/or the experimental duration. Indeed, feeding chicks for seven days with a diet containing 1600 μg AFB1/kg from A. flavus (NRRL 6540; CECT 2687) led to the deposition of 1.63, 0.49, and 0.41 μg/kg of AFB1 in muscles at 14, 21, and 28 days of age, respectively [10], thereby indicating that younger chicks accumulated more AFB1 than did older birds.
Broilers fed a diet containing 40 μg AFB1/kg (produced by a local Chinese strain of A. flavus) for 21 days, 50 μg AFB1/kg (produced by A. parasiticus, NRRL 2999) for 28 days, 50 μg AFB1/kg (produced by a local Thailand strain of A. flavus) for 39 days, or 250 μg AFB1/kg (produced by A. flavus, KP 137700) for 39 days accumulated concentrations of 11.48, 0.40, 0.1, and 12.8 μg AFB1/kg in the liver, respectively [25,26,27,28]. The hepatic accumulation of AFB1 in broilers was 0.17 μg/kg after they consumed feed containing 1000 μg AFB1/kg in the pure crystal form for seven weeks [52], whereas a similar concentration of AFB1 produced by A. flavus (NRRL 3357) led to the deposition of 0.33 μg AFB1/kg in chicken livers after feeding the contaminated diet for 28 days [30]. In addition, increasing the level of AFB1 from a pure source five-fold (5000 μg AFB1/kg) for 18 days led to the accumulation of less AFB1 in the liver (0.11 μg/kg) [53] compared with the levels detected by Denli et al. [52] (0.17 μg AFB1/kg) and Rajput et al. (0.33 μg AFB1/kg) [30], thereby indicating that the concentration of AFB1 is not the only major factor that determines the effect of AFB1 and its accumulation in edible poultry parts; the fungal strain producing the toxin may, instead, be the main factor. In addition to the risks associated with the detection of AFB1 in the edible parts of poultry, the presence of malondialdehyde (MDA) may be more hazardous than AFB1 to human health. MDA is recognized as being a carcinogenic substrate because it reacts with DNA to induce mutations, which can lead to cancer, especially hepatic cancer [54,55]. In general, the concentrations of MDA in poultry meat and the edible parts may be elevated irrespective of whether the AFB1 level in the diet is low (22 μg/kg) or high (2500 μg/kg) [30,48,56,57].

2.3. Bones

Tibial length, weight, strength, and mineralization are used to evaluate the bone quality in meat-type and egg-type birds [58,59]. In meat-type birds, bones are the main structures that will support the meat yield, so poor bone quality will lead to the appearance of leg problems during the finishing period, thereby hindering skeletal muscle development (constraining their genetic potential) and broken bones may occur after slaughter, adversely affecting carcass appearance and consumer acceptance [60]. In egg-type birds, almost one-third of the calcium (Ca) used for eggshell comes from bones because the Ca required for eggshell formation is not met solely by dietary sources [61]. Bones, therefore, represent calcium stores and poor bone quality is associated with bone weakness, low productivity, low eggshell quality, and economic losses [62]. Huff et al. [63] found that contamination of broiler diet during the first 3 weeks of age with 500 μg AFB1/kg generated by A. parasiticus (NRRL 2999) decreased tibial diameter and strength. Reduction of tibial strength in birds fed a diet containing AFB1 produced by A. parasiticus (NRRL 2999) may be from reduced deposition of Ca, phosphorus (P), zinc, and manganese in the tibia [64]. An association has been observed [65] between the concentration of AFB1 in the diet and the concentration of AFB1 in eggs. Therefore, AFB1 has been injected directly into fertilized eggs to save money, time, and effort when determining its effects. For instance, the injection of 0.04 μg AFB1/egg suppressed tibial growth (weight and length), which was linked to reduced hatchling weight and increased yolk sac weight [66]. Similar findings in terms of the tibial weight and length, embryo weight at 18 days of incubation, and the yolk sac weight were confirmed after injecting 0.05 μg AFB1 per egg [67]. The suppression of tibial growth could be due to the weak proliferation and hypertrophy of the growth plates, which are measured to evaluate bone development [66]. It was shown [68] that depressed skeletal development affected muscle development, where the embryo weight, and the weights of leg and breast muscle, decreased significantly at different stages of embryo development after the injection of 0.04 μg AFB1/egg; these were a consequence of suppressed cell proliferation and reduced number of myotube nuclei, thereby explaining the depressed muscle development and increased yolk sac weight in embryos from eggs injected with AFB1. The meat and egg yield will be affected in chicks that exhibit poor development during different stages of embryonic development. In broiler chickens that ingested a diet contaminated naturally with 82 and 134 μg AFB1/kg during the starter and grower phases [69], depressed growth rate and reduced tibial strength were associated with reduced ash, Ca, and P concentrations in the tibia. These were caused by suppressed production of 1,25-dihydroxycalciferol (which decreases Ca and P concentrations in blood and reduces tibial deposition of Ca and P) and the stimulation of parathyroid hormone (which activates osteoclasts to release calcium and organic components from bone and consequently weakening the bone). Reductions in weight gain, Ca concentrations, tibial weight, and tibial mineralization were found [70] in broilers fed a diet containing 2000 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for 21 days.

2.4. Immune Organs

Absolute and relative weights of immune organs are used to indirectly assess the immune status of birds; changes in their relative weights may result in altered in immune function. Table 2 summarizes the effects of AFB1 produced by A. flavus and A. parasiticus strains on the relative weights of the spleen, thymus, and bursa of Fabricius in poultry. In some studies [71], while the relative weights of the immune organs were not significantly affected by AFB1, histological changes in the organs were observed. Thus, the histological changes might not have been sufficient to cause significant reductions in the relative weights of the immune organs. In general, the suppression of lymphoid organ growth induced by AFB1 is related to reduced numbers of lymphocytes [72,73,74]. It has been reported [73,75] that the reduction in the relative weight of the bursa induced by AFB1 can be attributed to the decreased diameter of the lymphoid follicles and the reduced number of lymphocytes. In addition, increased relative weight of the spleen induced by AFB1 may be caused by the presence of congested red pulp in the organ [76], while reduced relative weight of the spleen caused by AFB1 may occur because its white pulp contains less lymphoid tissue [77]. These findings indicate that the lymphoid organs differ in terms of their sensitivity to AFB1, with the spleen being the most sensitive, followed by the bursa of Fabricius and thymus, possibly because the spleen receives and accumulates more AFB1 than the others [25]. AFB1 can suppress the activities of antioxidant enzymes and elevate content of MDA in the spleen, bursa, and thymus to cause oxidative damage, cell necrosis, and an increase in apoptosis [73,78,79]. This could account for AFB1 decreasing relative weights of the immune organs, thereby leading to their malfunction. It is not surprising, therefore, that significant declines in the production of antibodies, including IgA, IgG, and IgM, as well as the proportions of T and B lymphocytes, were found in broiler fed diets containing 40 μg AFB1/kg from A. flavus [25] and 1000 μg AFB1/kg produced by A. flavus (NRRL 3357) [30]. In addition, contaminating the maternal diet with 5000 μg AFB1/kg from A. flavus (NRRL 6540; CECT 2687) for three weeks significantly decreased the synthesis of IgA, IgG, and IgM in offspring chickens aged 21 days despite their being fed an AFB1-free diet [80]. Furthermore, the antibody titers against sheep red blood cells, Newcastle disease virus, and avian influenza (H5N1) were decreased by poultry diets contaminated with AFB1 [34,47,48,81,82].

2.5. Pancreas

The pancreas produces and secretes the digestive enzymes required to intestinally degrade feed and release nutrients to support the growth of birds, so they can express their genetic potential. A low concentration of AFB1 (20 μg/kg) produced by A. flavus (CICC 2219) in the diet of Cherry Valley ducks for six weeks led to a significant increase in the relative weight of the pancreas [50]. In contrast, 100 μg AFB1/kg from A. parasiticus (NRRL 2999) in the diet of broiler breeders for one month had no effect on the pancreas [84], but 300 μg AFB1/kg obtained from this same strain led to pancreatic hypertrophy [64]. The increased relative weight of the pancreas caused by AFB1 may be due to the high quantity of mature crystalline granules in the pancreatic cells [85]. The abnormal size of the pancreas in birds fed AFB1 may affect its functions, where the amylase, lipase, protease, chymotrypsin, and trypsin activities were elevated according to some studies [50,86,87,88], which would normally be expected to enhance the digestion of nutrients. Despite increased activities of digestive enzymes, the apparent digestibility of crude protein decreased without change in apparent digestibility of other nutrients in Cherry Valley ducks [50]; in White Pekin ducks, however, apparent ileal digestible energy decreased and the apparent ileal digestible nitrogen did not change when birds were fed a diet containing 200 μg AFB1/kg from A. parasiticus (NRRL 2999) for two weeks [89]. Indeed, the increased activities of digestive enzymes may be deceptive because oxidative damage and injury to the pancreas could occur, thereby compromising integrity of pancreatic cells leading to the release of proenzymes [87]. The percentage of nitrogen and dry matter stored in birds fed a diet containing AFB1 were unchanged but the birds lost weight [1,90,91], thereby confirming that the increased activities of digestive enzymes were related to a physiological problem.

2.6. Intestine

The intestinal villus height, crypt depth, and the ratio of the villus height to the crypt depth (H/D) are measured to assess the ability of the intestine to absorb nutrients [92]. In laying hens, 1200 μg AFB1/kg produced by A. parasiticus (NRRL 2999) had no effect on the villus height but it reduced H/D ratio in the jejunum [90]. Villus height, crypt depth, and H/D were all reduced in laying quail fed a diet contaminated with 1500 μg AFB1/kg from A. parasiticus (NRRL 2999) [34]. In addition, dietary treatment with only 2.0 μg AFB1/kg synthesized by A. parasiticus (PTCC 5286) caused a significant reduction in the villus height, a significant increase in the crypt depth, and a decrease in the jejunal H/D in broilers [43,44]. In the jejunum, decreases in the number of absorptive cells, weakened cell integrity, lesions, increased apoptosis, and suppression of the cell cycle in phase G2/M were found when AFB1 was present in the diets of broilers [93,94,95,96,97,98]. These findings may be explained by the capacity of the intestine to accumulate AFB1; intestinal concentration of AFB1 18 μg/kg when the dietary level was 22 μg/kg [29]. This may explain why AFB1 leads to abnormal development of the intestine and subsequent intestinal malfunctions. In the small intestine, lesions and reduced numbers of goblet cells that produce mucin 2 [99] could facilitate invasion of the intestine by harmful bacteria and adversely affect immunity. Thus, the populations of Escherichia coli, Clostridium perfringens, and Gram-negative bacteria increased in the ileal digesta of chickens fed a diet containing 40 μg AFB1/kg produced by A. flavus for 42 days [98]. However, feeding for 28 days with a diet containing 2.0 μg AFB1/kg produced by A. parasiticus (PTCC 5286) in broilers led to the population being dominated by E. coli, Salmonella, Klebsiella, and total Gram-negative bacteria [43,44]. In laying quail, treatment with feed containing 1500 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for five weeks increased the numbers of coliforms, Salmonella, and E. coli in the cecum [34]. In addition, the numbers of IgA+ cells, and abundance of transcripts for antibodies (IgA, IgM, and IgG), as well as their production decreased in the small intestine of broilers fed a diet containing AFB1 [100,101]. The cecal tonsils are considered among the largest lymphoid organs in the gut-associated tissues of birds and they are linked with mucosal immunity. AFB1 led to the appearance of lesions in the absorptive cells and decreased numbers of lymphocytes in the lymphatic nodules of the cecal tonsils [102]. The numbers of IgA+ cells, T cells, and their subsets (CD3+, CD3+CD4+, and CD3+CD8+), as well as the transcripts for antibodies (IgA, IgM, and IgG) and cytokines (interleukin 2 (IL2), tumor necrosis factor alpha (TNFα), and interferon (IFN-γ)) were also reduced in the cecal tonsils of chickens after consuming feed contaminated with AFB1 [102,103]. The appearance of lesions, fewer absorptive cells, increases in harmful bacteria, suppression of mucosal immunity in the intestines of birds, and impaired intestinal functions could explain the retarded development of various organs in birds after consuming diets contaminated with AFB1.

2.7. Liver

The liver is the main organ that processes mycotoxins, detoxifies them, and protects the body against their toxic effects. The liver is a central organ for lipid, protein, and amino acid metabolism, and their utilization [104,105], and is also involved in the hydroxylation of cholecalciferol to 25-hydroxycholecalciferol via 25-hydroxylase [106]. This intermediate is the precursor of 1,25-dihydroxy cholecalciferol, the most potent form of vitamin D3. The morphological and histological changes caused by AFB1 in the liver can be expected to result in functional changes. Table 3 summarizes the effects of AFB1 produced by A. flavus and A. parasiticus strains on the relative weight of the liver in poultry. Abnormal liver size may be associated with liver malfunctions. AFB1 can cause imbalanced lipid metabolism, promoting lipid deposition in the enlarged liver [107,108], repress the activity of antioxidant enzymes and anti-inflammatory cytokines, enhance lipid peroxidation and pro-inflammatory cytokines, and increase hepatocyte apoptosis [53,109,110,111,112,113]. The usual deleterious effects of AFB1 on hepatocytes result in high concentrations of aspartate aminotransferase and alanine aminotransferase in poultry blood after feeding diets containing AFB1 [37,50,71,81,114]. Aspartate aminotransferase (found in mitochondria) and alanine aminotransferase (found in the cytoplasm) are involved in hepatic protein metabolism, and they can determine the cell integrity [115,116]. Thus, the plasma content of total protein, albumin, globulin, triglycerides, and cholesterol decreased in poultry fed diets containing AFB1 [28,30,71,83,108,117,118], thereby indicating diminished protein and lipid biogenesis, which could account for reduced productivity of poultry fed such diets.

2.8. Kidney

The kidney is involved in synthesizing the active form of vitamin D by converting 25-hydroxycholecalciferol into 1,25-hydroxycholecalciferol via 1-α-hydroxylase [106], as well as clearing blood of dangerous waste products of metabolism and participating in the maintenance of biochemical homeostasis in birds [118,119]. Due to these functions, the kidney is the main organ that accumulates AFB1 in poultry. In particular, the liver accumulated 8.3 μg AFB1/kg while the kidney accumulated 16.2 μg AFB1/kg when chicks were fed diets contaminated with 2500 μg AFB1/kg produced by A. parasiticus (NRRL 2999) from hatch to day 21 [120]. In broilers, the liver accumulated 11.5 μg AFB1/kg and the kidney accumulated 45.4 μg AFB1/kg when chicks consumed a diet containing 40 μg AFB1/kg produced by A. flavus during the first 21 days [25]. The experimental periods and bird ages were similar in these two studies [25,120], and it is interesting that the kidney accumulated more AFB1 (45.4 μg vs. 16.2 μg/kg) when the AFB1 concentration was lower in the diet (40 μg vs. 2500 μg/kg), although different fungal strains were used in the two studies. The capacity of the kidney to process and accumulate AFB1 is higher than that of the liver, thereby making it the main organ in birds for accumulating AFB1. As a consequence, it is one of the main organs exposed to oxidative damage from AFB1. The kidney contained higher levels of MDA than did liver (160 nmol vs. 70 nmol/g, and 133 nmol vs. 99 nmol/g) when the same strain of chicks with similar ages consumed diets containing 1000 and 150 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for a similar experimental period [121,122]. The proportion of apoptotic cells was found to increase in the kidneys of broilers fed a diet containing AFB1 [123]. Although AFB1 increased the percentage of apoptotic renal cells, kidney enlargement also occurred [24,71,83,117,118,122,124], possibly due to increases in the number of mesangial cells and thickness of the glomerular basement membrane, and distension of the tubular epithelium cells as a consequence of granular degeneration [122,124,125]. It is not surprising, therefore, that the concentrations of creatinine and uric acid increased in the blood, reliable indicators of renal dysfunction [126,127], of birds that ingested feed contaminated with AFB1 [71,124]. Thus, various findings indicate that AFB1 causes kidney malfunction, which could in turn explain the reduced levels of 1, 25-dihydroxycalciferol, Ca, and P in the blood of birds fed diets containing AFB1 [24,69,83,118], thereby accounting for the poor bone mineralization, tibial bone quality, and eggshell quality noted earlier. Indeed, malfunctions of the intestine, liver, and kidney occurred concurrently in poultry that consumed diets contaminated with AFB1.

2.9. Reproductive Organs

As described above, reducing the daily feed intake is the first response observed in poultry that consume diets containing AFB1; this may be sufficient to reduce the relative weights of various organs, including those of the reproductive tract. Indeed, the abundance of vascular tissues surrounding the testes and their diameter declined, while the color of the testes changed from white to yellow, and the relative weight of the testes was lower when roosters were fed diets containing 5, 10, and 20 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for eight weeks [128]. Similar results were obtained in male quail after consuming a diet containing 2500 μg AFB1/kg produced by A. parasiticus (PTCC 5286) for four weeks [48,129]. In addition, the concentration of testosterone in quail plasma that ingested only 2.5 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for three weeks was reduced to almost one-third of that of the controls [130]. The same change was found [128] in roosters fed a diet containing 5 μg AFB1/kg from A. parasiticus (NRRL 2999) for eight weeks, spermatogenesis was suppressed with increased the production of abnormal spermatozoa. The performance of birds obtained by artificial insemination using semen produced by male birds that ingested AFB1 in their diet has not been tested but we consider that their fertility could be impaired. Reduced ovarian weights, suppressed follicle development, and the presence of only small follicles were reported in laying hens and quail after consuming diets containing 3300 μg AFB1/kg from natural contamination or 10 μg AFB1/kg produced by A. parasiticus (NRRL 2999) for three or four weeks, respectively [131,132]. Poults required longer (3–7 weeks or more) to reach sexual maturity when they ingested a diet containing AFB1 compared with those on an AFB1-free diet [9]. The deposition of AFB1 in the eggs of layer breeder hens started from the fifth day when they consumed a diet containing AFB1 [80]. In embryos, AFB1 can bind with DNA to induce mutations by altering some bases in the promoter sequences of growth hormone regulated gene1 [42]. This may explain the low hatchability, high percentage of defective embryos, and high proportion of embryonic mortality found in layer breeder hens when fed a diet containing AFB1 for three weeks [46]. Therefore, the reproductive systems of male and female birds are susceptible to the effects of AFB1. The low levels of AFB1 allowable in poultry diets in some countries, such as China (10 μg AFB1/kg diet) [1,81,86] and the European Union (20 μg AFB1/kg diet) [133], could adversely affect the development of the reproductive system in both sexes to subsequently suppress their fertility and reproduction.

3. Nutritional Factors for Counteracting AFB1

3.1. Inorganic AFB1 Binders

Several materials have been tested as AFB1 binders. In chickens, adding 15 g of clinoptilolite, 5.0 g of hydrated sodium calcium aluminosilicate, or 5.0 to 7.5 g of bentonite/kg to a diet contaminated with AFB1 produced by A. parasiticus (NRRL 2999) at concentrations of 2000–2500 μg relieved the deleterious effects of AFB1 on performance [31,70,134,135], decreased the concentration of AFB1 from 8.3 μg to 1.5 μg/kg in liver [120], reduced extent of hepatic lesions, and increased protein synthesis [70]. Similarly, adding 7.5 g of bentonite/kg diet containing 600 μg AFB1/kg produced by A. flavus (NRRL 6540; CECT 2687) decreased the level of AFB1 from 1.21μg to 0.16 μg/kg in the liver [136]. In addition, adding 5.0 g of hydrated sodium calcium aluminosilicate/kg diet containing 2000 μg AFB1/kg from A.parasiticus (NRRL 2999) maintained the relative weight of the liver in broilers to that of birds on the AFB1-free diet [135]. In another study [25] with chickens fed a diet with 40 μg AFB1/kg produced by A. flavus, 3.0 g of hydrated sodium calcium aluminosilicate/kg decreased the hepatic accumulation of AFB1, increased the amount of AFB1 excreted, and reduced the relative weight of the liver, but it failed to maintain liver size to that with the AFB1-free diet. These findings suggest that the amount of the same AFB1 binder should be chosen according to the strain of fungus that produces AFB1 as well as the concentration of AFB1 in the diet. Thus, when the AFB1 produced by the same fungal strain and the animal model was not changed, the doses of different AFB1 binders that induced the same effect (binding AFB1 and protecting birds from its toxic effects) varied [31,60,135], probably due to differences in the efficiency of AFB1 binders. Therefore, a new option consisting of an AF nano-binder has been developed, where adding 2.5 g of nano-clay/kg diet contaminated with 110 μg AFB1/kg was more efficient at improving the productivity of turkeys by protecting the liver, kidney, and intestine, as well as for enhancing their functions compared with molecular clay [137,138]. In addition, adding nano-composite magnetic graphene oxide with chitosan (5.0 g/kg diet) decreased the concentration of AFB1 in the intestine from 18 μg to 6 μg/kg and increased body weight gain and FCR to the levels achieved with an AFB1-free diet when chickens consumed a diet contaminated with 22 μg AFB1/kg produced by A. parasiticus (FRR 2999) [29]. Nanoproducts are available on a commercial scale but their impacts on human health and the environment are not well understood; thus, alternative solutions are needed.

3.2. Organic AFB1 Binders

3.2.1. Yeast

It has been reported that the β-1-3 glucane and mannoproteins found in yeast cell walls can bind AFB1 [139]. In breeder hens, adding 100 mg of yeast cell walls (containing 26 g of β-glucan and 15 g of mannan-oligosaccharides/100 g) normalized the secretion of digestive enzymes such as lipase and chymotrypsin after birds consumed feed containing 1000 μg AFB1/kg formed by A. parasiticus (NRRL 2999) [84]. Yeast cell walls containing D-glucose (48.3%) and D-mannose (32.3%) at a level of 0.5 g/kg failed to affect the performance or immunity in chickens that consumed a diet containing 40 μg AFB1/kg produced by A. flavus [45]. Adding 1.5 g/kg Saccharomyces cerevisiae yeast cell walls to a diet containing 350 μg AFB1/kg in broilers restored the daily weight gain as well as enhancing the FCR and antibody production relative to birds given an AFB1-free diet [72]. Moreover, in broilers, the addition of 1.0 g/kg yeast (Pichia kudriavzevii) to a diet that contained 100 μg AFB1/kg produced by A. parasiticus (NRRL 2999) increased the final body weight and carcass yield, and reduced the concentration of AFB1 in the liver by 14% [140]. However, adding 0.5 or 1.0 g/kg of yeast (Trichosporon mycotoxinivorans) to diets contaminated with 100 or 600 μg AFB1/kg produced by A. flavus (NRRL 6540; CECT 2687) failed to bind the AFs [136]. Yeast was also effective when added to drinking water with 5 × 109 of Saccharomyces cerevisiae CECT 1891 cells/L drinking water for broilers fed a diet containing 1200 μg AFB1/kg produced by A. parasiticus (NRRL 2999), where it reduced the increase in the size of the liver, improved protein synthesis, and restored the growth performance [141]. In addition, brewing waste containing yeast cell walls counteracted AFB1 when 10 g/kg cell walls was added to a broiler diet contaminated with 2000 μg AFB1/kg produced by A. parasiticus (NRRL 2999); improved protein synthesis and the Ca level in the blood, decreased hepatic lesions, and increased growth rate were observed [142]. These results indicate that different yeasts with different cell wall components account for the varying results obtained in previous studies with different fungal strain and resistance of birds.

3.2.2. Probiotic

Other microorganisms, particularly bacteria, can also have important effects, for example 1.0 g/kg of probiotic (commercial product) added to a diet containing 250 μg AFB1/kg produced by A. flavus (KP137700) improved the antioxidant status, liver function, protein synthesis, and productive performance of broiler chickens compared with an AFB1-free diet. This treatment reduced the level of AFB1 from 12.8 to 2.9 μg/kg in the liver compared with the AFB1-contaminated diet [28]. Moreover, mixing similar amounts of Lactobacillus acidophilus, Lactobacillus plantarum, and Enterococcus faecium, and adding them to the diet at a level of 1.5 × 1010 cfu/kg enhanced the digestibility of nutrients and antibody production, decreased the concentrations of AFB1 in the liver (from 11.5–2.2 μg/kg) and immune organs, maintained the normal relative weights of the liver and immune organs, and improved the performance of broilers fed a diet contaminated with 40 μg AFB1/kg produced by A. flavus [25]. Similarly, Bacillus subtilis (ANSB060) could detoxify AFB1, where 2.0 g/kg added to a broiler diet containing 70 μg AFB1/kg produced from moldy peanut meal decreased the accumulation of AFB1 from 7 to 1.5 μg/kg in the intestine and from 0.24 to 0.09 μg/kg in the liver, as well as reducing hepatic lipid peroxidation and enhancing liver functions, average daily gain, and FCR [143,144]. In ducks, adding 1.0 g/kg of Bacillus subtilis (ANSB060) to the diet was sufficient to counteract the toxicity of 22 μg AFB1/kg formed from moldy corn, where it increased the activity of antioxidant enzymes, improved FCR, and reduced AFB1 concentration from 0.12 to 0.06 μg/kg in the liver [56]. In laying hens, a combination of two strains of Bacillus subtilis (ANSB060 and ANSB01G) reduced the amount of the bacterium required to neutralize AFB1; 1.0 g/kg of the mixture improved laying performance, and delayed the appearance and concentration of AFB1 in the eggs, when hens consumed a diet contaminated with 123 μg AFB1/kg formed from moldy peanuts and corn meal [145]. In quail, 108 cfu of Berevibacillus laterosporus/mL of drinking water decreased hepatic necrosis and enhanced liver function, protein production, antibody levels, growth rate, and meat yield when fed a diet containing 2500 μg AFB1/kg produced by A. parasiticus (PTCC 5286) [47]. In broiler chickens, adding 108 cfu/mL of Lactobacillus plantarum 299v to drinking water increased the activity of antioxidant enzymes, reduced lipid peroxidation, and enhanced protein synthesis and the final body weight gain when they fed a diet containing 200–2000 μg AFB1/kg synthesized by A. parasiticus (PTCC 5286) [146]. Quail are more sensitive to AFB1 than are broiler chickens [5,38], but when the fungal strain that produced AFB1 and concentrations of the two probiotic bacteria were the same, it was shown [47] that Berevibacillus laterosporus counteracted the toxicity of 2500 μg AFB1, whereas Lactobacillus plantarum 299v [146] could only efficiently counteract the toxicity of 200 μg AFB1. These and other findings, therefore, suggest that the presence of one or more probiotic bacterial strains at particular optimized concentrations can efficiently counteract the toxicity of AFB1, again varying with the fungal strain and susceptibility of specific birds. Probiotic bacteria (organic AFB1 binder) and clay (inorganic AFB1 binder) [25] but not yeast cell walls (organic AFB1 binder) [45] restored the productivity and immunity in broilers fed diets containing the same level of AFB1 produced from the same fungus during the same experimental period, but the probiotic bacteria (organic AFB1 binder) were more efficient than clay (inorganic AFB1 binder) in reducing the concentrations of AFB1 in the liver, kidney, and lymphoid organs.

3.3. Antioxidants

As discussed above, birds exposed to AFB1 toxicity reduce their feed consumption, and thereby may not consume adequate amounts of dietary antioxidants for the effective functioning of the antioxidant defense system. In addition, AFB1 activates the formation of reactive oxygen species and free radicals to higher levels than the body can eliminate, thereby increasing lipid peroxidation and causing oxidative damage to most of the bodily organs. Therefore, providing antioxidants to poultry exposed to AFB1 might help support the antioxidant defense system, and improve productivity of poultry. In particular, adding 0.4 mg/kg selenium (Se) to diets enhanced the antioxidant defense system in the lymphoid organs [79,147,148,149,150], jejunum [97], and kidney [125], and protected against oxidative damage when chickens were fed diets containing 600 μg of AFB1/kg. Adding 300 μg/kg of alpha-lipoic acid alleviated the oxidative damage induced in the liver and kidney by AFB1 74 μg/kg produced by moldy peanut meal and 300 μg/kg produced by A. parasiticus (NRRL 2999) [77,151], where it restored the levels of IL-6, IFN-γ, and TNFα in the blood, and their transcript abundance in the liver of chickens [112]. The addition of 300 mL of Urtica diocia seed extract/kg of diet containing 1000 μg AFB1/kg produced by A. parasiticus (NRRL 2999) enhanced the antioxidant status, reduced hepatic and renal lipid peroxidation, and decreased the reduction in final body weight due to AFB1 [122]. Including 250 mg of grape seed proanthocyanidin extract/kg in a diet containing 1000 μg AFB1/kg produced by A. flavus (NRRL 3357) increased the antioxidant enzyme activity, decreased lipid peroxidation, reduced the accumulation of AFB1 (0.35 vs. 0.18 μg/kg) in the liver, improved the synthesis of proteins including IgA, IgG, and IgM, and mitigated the reduced productivity of broiler chickens [30]. In addition, adding 74 mg/kg curcuminoids or 150 mg/kg curcumin to a broiler diet containing 1000 μg AFB1/kg produced by A. parasiticus (NRRL 2999) or 100 μg AFB1/kg as the pure crystal form reduced the increase in the relative weight of the liver and decreased the levels of alanine aminotransferase, aspartate aminotransferase, and lipid peroxidation, increased the antioxidant capacity and protein production, and offset the reduced average daily gain [109,152]. These results show that antioxidants are required by poultry exposed to AFB1 in order to enhance the efficiency of the antioxidant defense system; this might involve altering AFB1 metabolism to alleviate its toxicity. Thus, adding an antioxidant such as grape seed proanthocyanidin extract decreased the accumulation of AFB1 in the liver from 0.35 to 0.18 μg/kg [30]. Curcumin or selenium could suppress the transcription and activities of cytochrome P450 isozymes (essential enzymes for converting AFB1 into the more toxic form (AFBO)), where they decreased the levels of 8-hydroxydeoxyguanosine (which can destroy DNA) and the formation of AFBO–DNA adducts in the livers of chickens exposed to AFB1 in the diet [152,153]. Probiotics can improve the antioxidant status in broilers exposed to AFB1 by binding the toxin to decrease the hepatic formation of its more toxic form (AFBO) by downregulating transcription of cytochrome P450 isozymes [28]. Therefore, adding antioxidants and an AFB1 binder together could be more effective than adding individual treatments for overcoming the effects of AFB1 in poultry. However, dietary supplementation with 7.5 g/kg bentonite clay alone in a diet containing 2000 μg AFB1/kg produced by A. parasiticus (NRRL 2999) was better than a combination of 200 mg curcuminoids and 7.5 g/kg bentonite clay [70], although the combination of 74 mg curcuminoids and 5 g/kg hydrated sodium calcium aluminosilicate in a diet containing 1000 μg AFB1/kg produced by A. parasiticus (NRRL 2999) was better than adding 5 g/kg hydrated sodium calcium aluminosilicate in broilers [154]. The concentrations of curcuminoids and AFB1 binder, as well as the concentration of AFB1 in the diets differed in these studies, which could explain the different results obtained. The concentration of AFB1, the fungal strain that produces AFB1, and the efficiency of the AFB1 binder with or without added antioxidants all should be considered in further studies to determine the best methods for eliminating AFB1. However, Table 4 summarizes the concentrations of some additives used in poultry diets to counteract the toxicity of AFB1. Figure 1 summarizes the impacts of AFB1 on the functions of organs and productivity in poultry, as well as on the health of consumers, and the nutritional factors that might mitigate these impacts.

4. Conclusions

The concentration of AFB1 is a key factor related to the occurrence of aflatoxicosis in poultry but the fungal strain that produces AFB1 should also be considered. In particular, AFB1 produced by specific fungal strains can have highly deleterious impacts on poultry productivity even when concentration of the toxin is low. The reductions in productivity and reproductive performance induced in poultry by AFB1 are the consequence of malfunctions in most of the organs in poultry due to AFB1. Nutritional factors such as inorganic and organic AFB1 binders, as well as antioxidants, vary in terms of their efficiency and the mechanism involved when counteracting the deleterious impacts of AFB1 on poultry. In particular, binding AFB1, decreasing the formation of AFBO, maintaining a strong antioxidant defense system, protecting the organs against oxidative damage, and maintaining organ functions should be considered when selecting anti-AFB1 additives. It is necessary to develop new additives or combinations to more efficiently counteract the deleterious effects of AFB1 and restore poultry productivity.

Author Contributions

A.M.F. wrote the manuscript. A.M.F., D.R., H.K.E.-S., W.C., S.J., and C.Z. contributed to the discussion. C.Z. conceived this project. All authors read and approved the final manuscript.

Funding

This work was supported by the Fund for National Key Research and Development Program (grant no. 2018YFD0501504, 2018YFD0500600), China Agricultural Research System (CARS-42-13), the Science and Technology Program for Pearl River Nova of Guangzhou City (grant no. 201710010159), President Foundation of Guangdong Academy of Agricultural Sciences (201808B), and the Science and Technology Program of Guangdong Province (2016A020210043).

Conflicts of Interest

All authors declare no conflict of interest.

References

  1. Abbasi, F.; Liu, J.; Zhang, H.; Shen, X.; Luo, X. Effects of feeding corn naturally contaminated with aflatoxin on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of Na+, K+-ATPase in ducklings. Asian-Aust. J. Anim. Sci. 2018, 31, 91–97. [Google Scholar] [CrossRef] [PubMed]
  2. Abdallah, M.F.; Girgin, G.; Baydar, T.; Krska, R.; Sulyok, M. Occurrence of multiple mycotoxins and other fungal metabolites in animal feed and maize samples from Egypt using LC-MS/MS. J. Sci. Food Agric. 2017, 97, 4419–4428. [Google Scholar] [CrossRef]
  3. Streit, E.; Naehrer, K.; Rodrigues, I.; Schatzmayr, G. Mycotoxin occurrence in feed and feed raw materials worldwide-long term analysis with special focus on Europe and Asia. J. Sci. Food Agric. 2013, 93, 2892–2899. [Google Scholar] [CrossRef]
  4. Guerre, P. Worldwide mycotoxins exposure in pig and poultry feed formulations. Toxins 2016, 8, 350. [Google Scholar] [CrossRef]
  5. Arafa, A.S.; Bloomer, R.J.; Wilson, H.R.; Simpson, C.F.; Harms, R.H. Susceptibility of various poultry species to dietary aflatoxin. Br. Poult. Sci. 1981, 22, 431–436. [Google Scholar] [CrossRef] [PubMed]
  6. Sweeney, M.J.; Dobson, A.D.W. Mycotoxin production by Aspergillus, Fusarium and Penicillium species. Int. J. Food Microbiol. 1998, 43, 141–158. [Google Scholar] [CrossRef]
  7. Pitt, J.I.; Miller, J.D. A concise history of mycotoxin research. J. Agric. Food Chem. 2017, 65, 7021–7033. [Google Scholar] [CrossRef] [PubMed]
  8. Oliveira, C.F.; Rosmaninho, J.F.; Castro, A.L.; Butkeraitis, P.; Reis, T.A.; Corrêa, B. Aflatoxin residues in eggs of laying Japanese quail after long-term administration of rations containing low levels of aflatoxin B1. Food Addit. Contam. 2003, 20, 648–653. [Google Scholar] [CrossRef]
  9. Pandey, I.; Chauhan, S.S. Studies on production performance and toxin residues in tissues and eggs of layer chickens fed on diets with various concentrations of aflatoxin AFB1. Br. Poult. Sci. 2007, 48, 713–723. [Google Scholar] [CrossRef] [PubMed]
  10. Hussain, Z.; Khan, M.Z.; Khan, A.; Javed, I.; Saleemi, M.K.; Mahmood, S.; Asi, M.R. Residues of aflatoxin B1 in broiler meat: Effect of age and dietary aflatoxin B1 levels. Food Chem. Toxicol. 2010, 48, 3304–3307. [Google Scholar] [CrossRef] [PubMed]
  11. Khlangwiset, P.; Shephard, G.S.; Wu, F. Aflatoxins and growth impairment: A review. Crit. Rev. Toxicol. 2011, 41, 740–755. [Google Scholar] [CrossRef] [PubMed]
  12. De Ruyck, K.; De Boevre, M.; Huybrechts, I.; De Saeger, S. Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. Mutat. Res. Rev. Mutat. Res. 2015, 766, 32–41. [Google Scholar] [CrossRef] [PubMed]
  13. Wu, F.; Groopman, J.D.; Pestka, J.J. Public health impacts of foodborne mycotoxins. Annu. Rev Food Sci. Technol. 2014, 5, 351–372. [Google Scholar] [CrossRef] [PubMed]
  14. Lesnierowski, G.; Stangierski, J. What’s new in chicken egg research and technology for human health promotion? A review. Trends Food Sci. Technol. 2018, 71, 46–51. [Google Scholar] [CrossRef]
  15. Drewnowski, A. The Nutrient Rich Foods Index helps to identify healthy, affordable foods. Am. J. Clin. Nutr. 2010, 91, 1095S–1101S. [Google Scholar] [CrossRef] [PubMed][Green Version]
  16. Al-Khalifa, H.; Al-Naser, A. Ostrich meat: Production, quality parameters, and nutritional comparison to other types of meats. J. Appl. Poult. Res. 2014, 23, 784–790. [Google Scholar] [CrossRef]
  17. Paleari, M.A.; Camisasca, S.; Beretta, G.; Renon, P.; Corsico, P.; Bertolo, G.; Crivelli, G. Ostrich meat: Physico-chemical characteristics and comparison with turkey and bovine meat. Meat Sci. 1998, 8, 205–210. [Google Scholar] [CrossRef]
  18. Zdanowska-Sąsiadek, Ż.; Marchewka, J.; Horbańczuk, J.O.; Wierzbicka, A.; Lipińska, P.; Jóźwik, A.; Atanasov, A.G.; Huminiecki, Ł.; Sieroń, A.; Sieroń, K.; et al. Nutrients Composition in Fit Snacks Made from Ostrich, Beef and Chicken Dried Meat. Molecules 2018, 23, 1267. [Google Scholar] [CrossRef] [PubMed]
  19. Barbut, S. Convenience breaded poultry meat products–New developments. Trends Food Sci. Technol. 2012, 26, 14–20. [Google Scholar] [CrossRef]
  20. Valverde, D.; Laca, A.; Estrada, L.N.; Paredes, B.; Rendueles, M.; Díaz, M. Egg yolk fractions as basic ingredient in the development of new snack products. Int. J. Gastron. Food Sci. 2016, 3, 23–29. [Google Scholar] [CrossRef][Green Version]
  21. Huang, X.; Ahn, D.U. How Can the Value and Use of Egg Yolk Be Increased? J. Food Sci. 2019. [Google Scholar] [CrossRef] [PubMed]
  22. Organization for Economic Co-operation and Development (OECD). Table 3A1.4. World Meat Projections. OECD-FAO Agricultural Outlook 2017–2026. Available online: https://doi.org/10.1787/agr_outlook-2017-table70-en (accessed on 6 February 2019).
  23. European Commission. Commission Regulation (EU) No 165/2010 of 26 February 2010 amending Regulation (EC) No 1881/2006 setting maximum levels for certain contaminants in foodstuffs as regards aflatoxins. Off. J. Eur. Union 2010, L50/8–L50/12. [Google Scholar]
  24. Kim, J.G.; Lee, Y.W.; Kim, P.G.; Roh, W.S.; Shintani, H. Reduction of aflatoxins by Korean soybean paste and its effect on cytotoxicity and reproductive toxicity-part 3. Inhibitory effects of Korean soybean paste (Doen-jang) on aflatoxin toxicity in laying hens and aflatoxin accumulation in their eggs. J. Food Prot. 2003, 66, 866–873. [Google Scholar] [CrossRef] [PubMed]
  25. Liu, N.; Wang, J.; Deng, Q.; Gu, K.; Wang, J. Detoxification of aflatoxin B1 by lactic acid bacteria and hydrated sodium calcium aluminosilicate in broiler chickens. Livest. Sci. 2018, 208, 28–32. [Google Scholar] [CrossRef]
  26. Magnoli, A.P.; Monge, M.P.; Miazzo, R.D.; Cavaglieri, L.R.; Magnoli, C.E.; Merkis, C.I.; Cristofolini, A.L.; Dalcero, A.M.; Chiacchiera, S.M. Effect of low levels of aflatoxin B1 on performance, biochemical parameters, and aflatoxin B1 in broiler liver tissues in the presence of monensin and sodium bentonite. Poult. Sci. 2011, 90, 48–58. [Google Scholar] [CrossRef]
  27. Bintvihok, A.; Kositcharoenkul, S. Effect of dietary calcium propionate on performance, hepatic enzyme activities and aflatoxin residues in broilers fed a diet containing low levels of aflatoxin B1. Toxicon 2006, 47, 41–46. [Google Scholar] [CrossRef] [PubMed]
  28. Salem, R.; El-Habashi, N.; Fadl, S.E.; Sakr, O.A.; Elbialy, Z.I. Effect of probiotic supplement on aflatoxicosis and gene expression in the liver of broiler chicken. Environ. Toxicol. Pharmacol. 2018, 60, 118–127. [Google Scholar] [CrossRef]
  29. Saminathan, M.; Selamat, J.; Abbasi Pirouz, A.; Abdullah, N.; Zulkifli, I. Effects of Nano-Composite Adsorbents on the Growth Performance, Serum Biochemistry, and Organ Weights of Broilers Fed with Aflatoxin-Contaminated Feed. Toxins 2018, 10, 345. [Google Scholar] [CrossRef] [PubMed]
  30. Rajput, S.A.; Sun, L.; Zhang, N.; Mohamed Khalil, M.; Gao, X.; Ling, Z.; Zhu, L.; Khan, F.A.; Zhang, J.; Qi, D. Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents, Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B1. Toxins 2017, 9, 371. [Google Scholar] [CrossRef] [PubMed]
  31. Shannon, T.A.; Ledoux, D.R.; Rottinghaus, G.E.; Shaw, D.P.; Daković, A.; Marković, M. The efficacy of raw and concentrated bentonite clay in reducing the toxic effects of aflatoxin in broiler chicks. Poult. Sci. 2017, 96, 1651–1658. [Google Scholar] [CrossRef]
  32. Stanley, V.G.; Winsman, M.; Dunkley, C.; Ogunleye, T.; Daley, M.; Krueger, W.F.; Sefton, A.E.; Hinton Jr, A. The impact of yeast culture residue on the suppression of dietary aflatoxin on the performance of broiler breeder hens. J. Appl. Poult. Res. 2004, 13, 533–539. [Google Scholar] [CrossRef]
  33. Sakamoto, M.I.; Murakami, A.E.; Fernandes, A.M.; Ospina-Rojas, I.C.; Nunes, K.C.; Hirata, A.K. Performance and serum biochemical profile of Japanese quail supplemented with silymarin and contaminated with aflatoxin B1. Poult. Sci. 2018, 97, 159–166. [Google Scholar] [CrossRef] [PubMed]
  34. Manafi, M. Toxicity of aflatoxin B1 on laying Japanese quails (Coturnix coturnix japonica). J. Appl. Anim. Res. 2018, 46, 953–959. [Google Scholar] [CrossRef]
  35. Chen, X.; Horn, N.; Cotter, P.F.; Applegate, T.J. Growth, serum biochemistry, complement activity, and liver gene expression responses of Pekin ducklings to graded levels of cultured aflatoxin B1. Poult. Sci. 2014, 93, 2028–2036. [Google Scholar] [CrossRef] [PubMed]
  36. Rauber, R.H.; Dilkin, P.; Giacomini, L.Z.; de Almeida, C.A.; Mallmann, C.A. Performance of turkey poults fed different doses of aflatoxins in the diet. Poult. Sci. 2007, 86, 1620–1624. [Google Scholar] [CrossRef] [PubMed]
  37. Diaz, G.J.; Cortes, A.; Botero, L. Evaluation of the ability of a feed additive to ameliorate the adverse effects of aflatoxins in turkey poults. Br. Poult. Sci. 2009, 50, 240–250. [Google Scholar] [CrossRef] [PubMed]
  38. Lozano, M.C.; Diaz, G.J. Microsomal and cytosolic biotransformation of aflatoxin B1 in four poultry species. Br. Poult. Sci. 2006, 47, 734–741. [Google Scholar] [CrossRef] [PubMed]
  39. Diaz, G.J.; Murcia, H.W.; Cepeda, S.M. Cytochrome P450 enzymes involved in the metabolism of aflatoxin B1 in chickens and quail. Poult. Sci. 2010, 89, 2461–2469. [Google Scholar] [CrossRef] [PubMed]
  40. Gregorio, M.C.D.; Bordin, K.; Souto, P.C.M.D.C.; Corassin, C.H.; Oliveira, C.A.F. Comparative biotransformation of aflatoxin B1 in swine, domestic fowls, and humans. Toxin Rev. 2015, 34, 142–150. [Google Scholar] [CrossRef]
  41. Williams, J.G.; Deschl, U.; Williams, G.M. DNA damage in fetal liver cells of turkey and chicken eggs dosed with aflatoxin B1. Arch. Toxicol. 2011, 85, 1167–1172. [Google Scholar] [CrossRef]
  42. Gülbahçe Mutlu, E.; Arslan, E.; Öznurlu, Y.; Özparlak, H. The effects of aflatoxin B1 on growth hormone regulated gene-1 and interaction between DNA and aflatoxin B1 in broiler chickens during hatching. Biotech. Histochem. 2018, 93, 463–470. [Google Scholar] [CrossRef] [PubMed]
  43. Jahanian, E.; Mahdavi, A.H.; Asgary, S.; Jahanian, R. Effect of dietary supplementation of mannanoligosaccharides on growth performance, ileal microbial counts, and jejunal morphology in broiler chicks exposed to aflatoxins. Livest. Sci. 2016, 190, 123–130. [Google Scholar] [CrossRef]
  44. Jahanian, E.; Mahdavi, A.H.; Asgary, S.; Jahanian, R. Effects of dietary inclusion of silymarin on performance, intestinal morphology and ileal bacterial count in aflatoxin-challenged broiler chicks. J. Anim. Physiol. Anim. Nutr. 2017, 101, e43–e54. [Google Scholar] [CrossRef] [PubMed]
  45. Liu, N.; Wang, J.Q.; Jia, S.C.; Chen, Y.K.; Wang, J.P. Effect of yeast cell wall on the growth performance and gut health of broilers challenged with aflatoxin B1 and necrotic enteritis. Poult. Sci. 2018, 97, 477–484. [Google Scholar] [CrossRef] [PubMed]
  46. Khan, W.A.; Khan, M.Z.; Khan, A.; Hassan, Z.U.; Rafique, S.; Saleemi, M.K.; Ahad, A. Dietary vitamin E in White Leghorn layer breeder hens: A strategy to combat aflatoxin B1-induced damage. Avian Pathol. 2014, 43, 389–395. [Google Scholar] [CrossRef] [PubMed]
  47. Bagherzadeh Kasmani, F.; Karimi Torshizi, M.A.; Allameh, A.; Shariatmadari, F. A novel aflatoxin-binding Bacillus probiotic: Performance, serum biochemistry, and immunological parameters in Japanese quail. Poult. Sci. 2012, 91, 1846–1853. [Google Scholar] [CrossRef][Green Version]
  48. Rasouli-Hiq, A.A.; Bagherzadeh-Kasmani, F.; Mehri, M.; Karimi-Torshizi, M.A. Nigella sativa (black cumin seed) as a biological detoxifier in diet contaminated with aflatoxin B1. J. Anim. Physiol. Anim. Nutr. 2017, 26, 229–238. [Google Scholar] [CrossRef]
  49. Mahmood, S.; Younus, M.; Aslam, A.; Anjum, A.A. Toxicological effects of aflatoxin B1 on growth performance, humoral immune response and blood profile of Japanese quail. J. Anim. Plant Sci. 2017, 27, 833–840. [Google Scholar]
  50. Han, X.Y.; Huang, Q.C.; Li, W.F.; Jiang, J.F.; Xu, Z.R. Changes in growth performance, digestive enzyme activities and nutrient digestibility of cherry valley ducks in response to aflatoxin B1 levels. Livest. Sci. 2008, 119, 216–220. [Google Scholar] [CrossRef]
  51. Hassan, Z.U.; Khan, M.Z.; Khan, A.; Javed, I.; Hussain, Z. Effects of individual and combined administration of ochratoxin A and aflatoxin B1 in tissues and eggs of White Leghorn breeder hens. J. Sci. Food Agric. 2012, 92, 1540–1544. [Google Scholar] [CrossRef]
  52. Denli, M.; Blandon, J.C.; Guynot, M.E.; Salado, S.; Perez, J.F. Effects of dietary AflaDetox on performance, serum biochemistry, histopathological changes, and aflatoxin residues in broilers exposed to aflatoxin B1. Poult. Sci. 2009, 88, 1444–1451. [Google Scholar] [CrossRef] [PubMed]
  53. Wang, X.H.; Li, W.; Wang, X.H.; Han, M.Y.; Muhammad, I.; Zhang, X.Y.; Sun, X.Q.; Cui, X.X. Water-soluble substances of wheat: A potential preventer of aflatoxin B1-induced liver damage in broilers. Poult. Sci. 2019, 98, 136–149. [Google Scholar] [CrossRef] [PubMed]
  54. Goetz, M.E.; Luch, A. Reactive species: A cell damaging rout assisting to chemical carcinogens. Cancer Lett. 2008, 266, 73–83. [Google Scholar] [CrossRef] [PubMed]
  55. Klaunig, J.E.; Wang, Z.; Pu, X.; Zhou, S. Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol. Appl. Pharmacol. 2011, 254, 86–99. [Google Scholar] [CrossRef] [PubMed]
  56. Zhang, L.; Ma, Q.; Ma, S.; Zhang, J.; Jia, R.; Ji, C.; Zhao, L. Ameliorating effects of Bacillus subtilis ANSB060 on growth performance, antioxidant functions, and aflatoxin residues in ducks fed diets contaminated with aflatoxins. Toxins 2017, 9, 1. [Google Scholar] [CrossRef] [PubMed]
  57. Migliorini, M.J.; Da Silva, A.S.; Santurio, J.M.; Bottari, N.B.; Gebert, R.R.; Reis, J.H.; Volpato, A.; Morsch, V.M.; Baldissera, M.D.; Stefani, L.M.; et al. The Protective Effects of an Adsorbent against Oxidative Stress in Quails Fed Aflatoxin-Contaminated Diet. Acta Sci. Vet. 2017, 45, 1–7. [Google Scholar] [CrossRef]
  58. Julian, R.J. Production and growth related disorders and other metabolic diseases of poultry—A review. Vet. J. 2005, 169, 350–369. [Google Scholar] [CrossRef] [PubMed]
  59. Silversides, F.G.; Singh, R.; Cheng, K.M.; Korver, D.R. Comparison of bones of 4 strains of laying hens kept in conventional cages and floor pens. Poult. Sci. 2012, 91, 1–7. [Google Scholar] [CrossRef] [PubMed]
  60. Rath, N.C.; Huff, G.R.; Huff, W.E.; Balog, J.M. Factors regulating bone maturity and strength in poultry. Poult. Sci. 2000, 79, 1024–1032. [Google Scholar] [CrossRef] [PubMed]
  61. Mueller, W.J.; Schraer, R.; Scharer, H. Calcium metabolism and skeletal dynamics of laying pullets. J. Nutr. 1964, 84, 20–26. [Google Scholar] [CrossRef] [PubMed]
  62. Whitehead, C.C. Overview of bone biology in the egg-laying hen. Poult. Sci. 2004, 83, 193–199. [Google Scholar] [CrossRef] [PubMed][Green Version]
  63. Huff, W.E.; Doerr, J.A.; Hamilton, P.B.; Hamann, D.D.; Peterson, R.E.; Ciegler, A. Evaluation of bone strength during aflatoxicosis and ochratoxicosis. Appl. Environ. Microbiol. 1980, 40, 102–107. [Google Scholar]
  64. Raju, M.V.L.N.; Rama Rao, S.V.; Radhika, K.; Panda, A.K. Effect of amount and source of supplemental dietary vegetable oil on broiler chickens exposed to aflatoxicosis. Br. Poult. Sci. 2005, 46, 587–594. [Google Scholar] [CrossRef]
  65. Sur, E.; Celik, I. Effects of aflatoxin B1 on the development of the bursa of Fabricius and blood lymphocyte acid phosphatase of the chicken. Br. Poult. Sci. 2003, 44, 558–566. [Google Scholar] [CrossRef]
  66. Oznurlu, Y.; Celik, I.; Sur, E.; Ozaydın, T.; Oğuz, H.; Altunbaş, K. Determination of the effects of aflatoxin B1 given in ovo on the proximal tibial growth plate of broiler chickens: Histological, histometric and immunohistochemical findings. Avian Pathol. 2012, 41, 469–477. [Google Scholar] [CrossRef]
  67. Yin, H.B.; Chen, C.H.; Darre, M.J.; Donoghue, A.M.; Donoghue, D.J.; Venkitanarayanan, K. Phytochemicals reduce aflatoxin-induced toxicity in chicken embryos. Poult. Sci. 2017, 96, 3725–3732. [Google Scholar] [CrossRef]
  68. Gündüz, N.; Oznurlu, Y. Adverse effects of aflatoxin B1 on skeletal muscle development in broiler chickens. Br. Poult. Sci. 2014, 55, 684–692. [Google Scholar] [CrossRef] [PubMed]
  69. Bai, S.; Wang, L.; Luo, Y.; Ding, X.; Yang, J.; Bai, J.; Zhang, K.; Wang, J. Effects of Corn Naturally Contaminated with Aflatoxins on Performance, Calcium and Phosphorus Metabolism, and Bone Mineralization of Broiler Chicks. J. Poult. Sci. 2013, 51, 157–164. [Google Scholar] [CrossRef][Green Version]
  70. Dos Anjos, F.R.; Ledoux, D.R.; Rottinghaus, G.E.; Chimonyo, M. Efficacy of adsorbents (bentonite and diatomaceous earth) and turmeric (Curcuma longa) in alleviating the toxic effects of aflatoxin in chicks. Br. Poult. Sci. 2015, 56, 459–469. [Google Scholar] [CrossRef] [PubMed]
  71. Gómez-Espinosa, D.; Cervantes-Aguilar, F.J.; Del Río-García, J.C.; Villarreal-Barajas, T.; Vázquez-Durán, A.; Méndez-Albores, A. Ameliorative Effects of Neutral Electrolyzed Water on Growth Performance, Biochemical Constituents, and Histopathological Changes in Turkey Poults during Aflatoxicosis. Toxins 2017, 9, 104. [Google Scholar] [CrossRef] [PubMed]
  72. Mendieta, C.R.; Gómez, G.V.; Del Río, J.C.G.; Cuevas, A.C.; Arce, J.M.; Ávila, E.G. Effect of the addition of saccharomyces cerevisiae yeast cell walls to diets with mycotoxins on the performance and immune responses of broilers. J. Poult. Sci. 2018, 55, 38–46. [Google Scholar] [CrossRef]
  73. Yuan, S.; Wu, B.; Yu, Z.; Fang, J.; Liang, N.; Zhou, M.; Huang, C.; Peng, X. The mitochondrial and endoplasmic reticulum pathways involved in the apoptosis of bursa of Fabricius cells in broilers exposed to dietary aflatoxin B1. Oncotarget 2016, 7, 65295–65306. [Google Scholar] [CrossRef]
  74. Zhu, P.; Zuo, Z.; Zheng, Z.; Wang, F.; Peng, X.; Fang, J.; Cui, H.; Gao, C.; Song, H.; Zhou, Y.; et al. Aflatoxin B1 affects apoptosis and expression of death receptor and endoplasmic reticulum molecules in chicken spleen. Oncotarget 2017, 8, 99531–99540. [Google Scholar]
  75. Bhatti, S.A.; Khan, M.Z.; Saleemi, M.K.; Saqib, M.; Khan, A.; Ul-Hassan, Z. Protective role of bentonite against aflatoxin B1-and ochratoxin A-induced immunotoxicity in broilers. J. Immunotoxicol. 2017, 14, 66–76. [Google Scholar] [CrossRef] [PubMed]
  76. Peng, X.; Zhang, K.; Bai, S.; Ding, X.; Zeng, Q.; Yang, J.; Fang, J.; Chen, K. Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn. Int. J. Environ. Res. Public Health 2014, 11, 8567–8580. [Google Scholar] [CrossRef] [PubMed]
  77. Karaman, M.; Özen, H.; Tuzcu, M.; Ciğremiş, Y.; Önder, F.; Özcan, K. Pathological, biochemical and haematological investigations on the protective effect of α-lipoic acid in experimental aflatoxin toxicosis in chicks. Br. Poult. Sci. 2010, 51, 132–141. [Google Scholar] [CrossRef] [PubMed]
  78. Peng, X.; Bai, S.; Ding, X.; Zhang, K. Pathological impairment, cell cycle arrest and apoptosis of thymus and bursa of fabricius induced by aflatoxin-contaminated corn in Broilers. Int. J. Environ. Res. Public Health 2017, 14, 77. [Google Scholar] [CrossRef] [PubMed]
  79. Chen, K.; Shu, G.; Peng, X.; Fang, J.; Cui, H.; Chen, J.; Wang, F.; Chen, Z.; Zuo, Z.; Deng, J.; et al. Protective role of sodium selenite on histopathological lesions, decreased T-cell subsets and increased apoptosis of thymus in broilers intoxicated with aflatoxin B1. Food Chem. Toxicol. 2013, 59, 446–454. [Google Scholar] [CrossRef] [PubMed]
  80. Ul-Hassan, Z.; Zargham Khan, M.; Khan, A.; Javed, I. Immunological status of the progeny of breeder hens kept on ochratoxin A (OTA)-and aflatoxin B1 (AFB1)-contaminated feeds. J. Immunotoxicol. 2012, 9, 381–391. [Google Scholar] [CrossRef] [PubMed]
  81. He, J.; Zhang, K.Y.; Chen, D.W.; Ding, X.M.; Feng, G.D.; Ao, X. Effects of vitamin E and selenium yeast on growth performance and immune function in ducks fed maize naturally contaminated with aflatoxin B1. Livest. Sci. 2013, 152, 200–207. [Google Scholar] [CrossRef]
  82. Tessari, E.N.C.; Oliveira, C.A.F.; Cardoso, A.L.S.P.; Ledoux, D.R.; Rottinghaus, G.E. Effects of aflatoxin B1 and fumonisin B1 on body weight, antibody titres and histology of broiler chicks. Br. Poult. Sci. 2006, 47, 357–364. [Google Scholar] [CrossRef]
  83. Bailey, C.A.; Latimer, G.W.; Barr, A.C.; Wigle, W.L.; Haq, A.U.; Balthrop, J.E.; Kubena, L.F. Efficacy of montmorillonite clay (NovaSil PLUS) for protecting full-term broilers from aflatoxicosis. J. Appl. Poult. Res. 2006, 15, 198–206. [Google Scholar] [CrossRef]
  84. Matur, E.; Ergul, E.; Akyazi, I.; Eraslan, E.; Cirakli, Z.T. The effects of Saccharomyces cerevisiae extract on the weight of some organs, liver, and pancreatic digestive enzyme activity in breeder hens fed diets contaminated with aflatoxins. Poult. Sci. 2010, 89, 2213–2220. [Google Scholar] [CrossRef] [PubMed]
  85. Şimşek, N.; Ergun, L.; Ergun, E.; Alabay, B.; Essiz, D. The effects of experimental aflatoxicosis on the exocrine pancreas in quails (Coturnix coturnix japonica). Arch. Toxicol. 2007, 81, 583–588. [Google Scholar] [PubMed]
  86. Feng, G.D.; He, J.; Ao, X.; Chen, D.W. Effects of maize naturally contaminated with aflatoxin B1 on growth performance, intestinal morphology, and digestive physiology in ducks. Poult. Sci. 2017, 96, 1948–1955. [Google Scholar]
  87. Marchioro, A.; Mallmann, A.O.; Diel, A.; Dilkin, P.; Rauber, R.H.; Blazquez, F.J.H.; Oliveira, M.G.A.; Mallmann, C.A. Effects of aflatoxins on performance and exocrine pancreas of broiler chickens. Avian Dis. 2013, 57, 280–284. [Google Scholar]
  88. Chen, X.; Naehrer, K.; Applegate, T.J. Interactive effects of dietary protein concentration and aflatoxin B1 on performance, nutrient digestibility, and gut health in broiler chicks. Poult. Sci. 2016, 95, 1312–1325. [Google Scholar] [CrossRef] [PubMed]
  89. Chen, X.; Murdoch, R.; Zhang, Q.; Shafer, D.J.; Applegate, T.J. Effects of dietary protein concentration on performance and nutrient digestibility in Pekin ducks during aflatoxicosis. Poult. Sci. 2016, 95, 834–841. [Google Scholar] [CrossRef] [PubMed][Green Version]
  90. Applegate, T.J.; Schatzmayr, G.; Pricket, K.; Troche, C.; Jiang, Z. Effect of aflatoxin culture on intestinal function and nutrient loss in laying hens. Poult. Sci. 2009, 88, 1235–1241. [Google Scholar] [CrossRef][Green Version]
  91. Yunus, A.W.; Razzazi-Fazeli, E.; Bohm, J. Aflatoxin B1 in affecting broiler’s performance, immunity, and gastrointestinal tract: A review of history and contemporary issues. Toxins 2011, 3, 566–590. [Google Scholar] [CrossRef] [PubMed]
  92. Yamauchi, K.E. Review on chicken intestinal villus histological alterations related with intestinal function. J. Poult. Sci. 2002, 39, 229–242. [Google Scholar] [CrossRef]
  93. Peng, X.; Zhang, S.; Fang, J.; Cui, H.; Zuo, Z.; Deng, J. Protective roles of sodium selenite against aflatoxin B1-induced apoptosis of jejunum in broilers. Int. J. Environ. Res. Public Health 2014, 11, 13130–13143. [Google Scholar] [CrossRef]
  94. Zheng, Z.; Zuo, Z.; Zhu, P.; Wang, F.; Yin, H.; Peng, X.; Fang, J.; Cui, H.; Gao, C.; Song, H.; et al. A study on the expression of apoptotic molecules related to death receptor and endoplasmic reticulum pathways in the jejunum of AFB1-intoxicated chickens. Oncotarget 2017, 8, 89655–89664. [Google Scholar] [CrossRef]
  95. Yin, H.; Jiang, M.; Peng, X.; Cui, H.; Zhou, Y.; He, M.; Zuo, Z.; Ouyang, P.; Fan, J.; Fang, J. The molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum. Oncotarget 2016, 7, 35592–35606. [Google Scholar] [CrossRef]
  96. Fang, J.; Zheng, Z.; Yang, Z.; Peng, X.; Zuo, Z.; Cui, H.; Ouyang, P.; Shu, G.; Chen, Z.; Huang, C. Ameliorative effects of selenium on the excess apoptosis of the jejunum caused by AFB1 through death receptor and endoplasmic reticulum pathways. Toxicol. Res. 2018, 7, 1108–1119. [Google Scholar] [CrossRef] [PubMed]
  97. Fang, J.; Yin, H.; Zheng, Z.; Zhu, P.; Peng, X.; Zuo, Z.; Cui, H.; Zhou, Y.; Ouyang, P.; Geng, Y.; et al. The molecular mechanisms of protective role of Se on the G2/M phase arrest of jejunum caused by AFB1. Biol. Trace Elem. Res. 2018, 181, 142–153. [Google Scholar] [CrossRef]
  98. Liu, N.; Wang, J.Q.; Liu, Z.Y.; Wang, Y.C.; Wang, J.P. Comparison of probiotics and clay detoxifier on the growth performance and enterotoxic markers of broilers fed diets contaminated with aflatoxin B1. J. Appl. Poult. Res. 2018, 27, 341–348. [Google Scholar] [CrossRef]
  99. Wang, F.; Zuo, Z.; Chen, K.; Gao, C.; Yang, Z.; Zhao, S.; Li, J.; Song, H.; Peng, X.; Fang, J.; et al. Histopathological Injuries, Ultrastructural Changes, and Depressed TLR Expression in the Small Intestine of Broiler Chickens with Aflatoxin B1. Toxins 2018, 10, 131. [Google Scholar] [CrossRef] [PubMed]
  100. He, Y.; Fang, J.; Peng, X.; Cui, H.; Zuo, Z.; Deng, J.; Chen, Z.; Geng, Y.; Lai, W.; Shu, G.; et al. Effects of sodium selenite on aflatoxin B1-induced decrease of ileal IgA+ cell numbers and immunoglobulin contents in broilers. Biol. Trace Elem. Res. 2014, 160, 49–55. [Google Scholar] [CrossRef] [PubMed]
  101. Jiang, M.; Fang, J.; Peng, X.; Cui, H.; Yu, Z. Effect of aflatoxin B1 on IgA+ cell number and immunoglobulin mRNA expression in the intestine of broilers. Immunopharmacol. Immunotoxicol. 2015, 37, 450–457. [Google Scholar] [CrossRef] [PubMed]
  102. Liu, C.; Zuo, Z.; Zhu, P.; Zheng, Z.; Peng, X.; Fang, J.; Cui, H.; Zhou, Y.; Ouyang, P.; Geng, Y.; et al. Sodium selenite prevents suppression of mucosal humoral response by AFB1 in broiler’s cecal tonsil. Oncotarget 2017, 8, 54215–54226. [Google Scholar] [PubMed]
  103. Wang, F.; Zuo, Z.; Chen, K.; Peng, X.; Fang, J.; Cui, H.; Shu, G.; He, M.; Tang, L. Selenium Rescues Aflatoxin B1-Inhibited T Cell Subsets and Cytokine Levels in Cecal Tonsil of Chickens. Biol. Trace Elem. Res. 2019, 188, 461–467. [Google Scholar] [CrossRef] [PubMed]
  104. Fouad, A.M.; El-Senousey, H.K. Nutritional factors affecting abdominal fat deposition in poultry: A review. Asian-Aust. J. Anim. Sci. 2014, 27, 1057–1068. [Google Scholar] [CrossRef] [PubMed]
  105. Hiramoto, K.; Muramatsu, T.; Okumura, J. Effect of methionine and lysine deficiencies on protein synthesis in the liver and oviduct and in the whole body of laying hens. Poult. Sci. 1990, 69, 84–89. [Google Scholar] [CrossRef]
  106. Shanmugasundaram, R.; Selvaraj, R.K. Vitamin D-1α-hydroxylase and vitamin D-24-hydroxylase mRNA studies in chickens. Poult. Sci. 2012, 91, 1819–1824. [Google Scholar] [CrossRef]
  107. Siloto, E.V.; Oliveira, E.F.A.; Sartori, J.R.; Fascina, V.B.; Martins, B.A.B.; Ledoux, D.R.; Rottinghaus, G.E.; Sartori, D.R.S. Lipid metabolism of commercial layers fed diets containing aflatoxin, fumonisin, and a binder. Poult. Sci. 2013, 92, 2077–2083. [Google Scholar] [CrossRef][Green Version]
  108. Tejada-Castaneda, Z.I.; Avila-Gonzalez, E.; Casaubon-Huguenin, M.T.; Cervantes-Olivares, R.A.; Vásquez-Peláez, C.; Hernandez-Baumgarten, E.M.; Moreno-Martínez, E. Biodetoxification of aflatoxin-contaminated chick feed. Poult. Sci. 2008, 87, 1569–1576. [Google Scholar] [CrossRef] [PubMed]
  109. Yarru, L.P.; Settivari, R.S.; Gowda, N.K.S.; Antoniou, E.; Ledoux, D.R.; Rottinghaus, G.E. Effects of turmeric (Curcuma longa) on the expression of hepatic genes associated with biotransformation, antioxidant, and immune systems in broiler chicks fed aflatoxin. Poult. Sci. 2009, 88, 2620–2627. [Google Scholar] [CrossRef]
  110. Ma, Q.G.; Gao, X.; Zhou, T.; Zhao, L.H.; Fan, Y.; Li, X.Y.; Lei, Y.P.; Ji, C.; Zhang, J.Y. Protective effect of Bacillus subtilis ANSB060 on egg quality, biochemical and histopathological changes in layers exposed to aflatoxin B1. Poult. Sci. 2012, 91, 2852–2857. [Google Scholar] [CrossRef] [PubMed]
  111. Liao, S.; Shi, D.; Clemons-Chevis, C.L.; Guo, S.; Su, R.; Qiang, P.; Tang, Z. Protective role of selenium on aflatoxin B1-induced hepatic dysfunction and apoptosis of liver in ducklings. Biol. Trace Elem. Res. 2014, 162, 296–301. [Google Scholar] [CrossRef]
  112. Ma, Q.; Li, Y.; Fan, Y.; Zhao, L.; Wei, H.; Ji, C.; Zhang, J. Molecular mechanisms of lipoic acid protection against aflatoxin B1-induced liver oxidative damage and inflammatory responses in broilers. Toxins 2015, 7, 5435–5447. [Google Scholar] [CrossRef]
  113. Muhammad, I.; Wang, X.; Li, S.; Li, R.; Zhang, X. Curcumin confers hepatoprotection against AFB1-induced toxicity via activating autophagy and ameliorating inflammation involving Nrf2/HO-1 signaling pathway. Mol. Biol. Rep. 2018, 45, 1775–1785. [Google Scholar] [CrossRef] [PubMed]
  114. Muhammad, I.; Wang, H.; Sun, X.; Wang, X.; Han, M.; Lu, Z.; Cheng, P.; Hussain, M.A.; Zhang, X. Dual role of dietary curcumin through attenuating AFB1-induced oxidative stress and liver injury via modulating liver phase-I and phase-II enzymes involved in AFB1 bioactivation and detoxification. Front. Pharmacol. 2018, 9, 554. [Google Scholar] [CrossRef] [PubMed]
  115. Walzem, R.L.; Simon, C.; Morishita, T.; Lowenstine, L.; Hansen, R.J. Fatty liver hemorrhagic syndrome in hens overfed a purified diet. Selected enzyme activities and liver histology in relation to liver hemorrhage and reproductive performance. Poult. Sci. 1993, 72, 1479–1491. [Google Scholar] [CrossRef] [PubMed]
  116. Jiang, S.; Hester, P.Y.; Hu, J.Y.; Yan, F.F.; Dennis, R.L.; Cheng, H.W. Effect of perches on liver health of hens. Poult. Sci. 2014, 93, 1618–1622. [Google Scholar] [CrossRef] [PubMed][Green Version]
  117. Şehu, A.; Cakir, S.; Cengiz, Ö.; Eşsiz, D. MYCOTOX® and aflatoxicosis in quails. Br. Poult. Sci. 2005, 46, 520–524. [Google Scholar] [CrossRef] [PubMed]
  118. Gholami-Ahangaran, M.; Rangsaz, N.; Azizi, S. Evaluation of turmeric (Curcuma longa) effect on biochemical and pathological parameters of liver and kidney in chicken aflatoxicosis. Pharm. Biol. 2016, 54, 780–787. [Google Scholar] [CrossRef] [PubMed]
  119. Sun, D.; Li, C.; Gao, J.; Li, S.; Wang, H. Effects of selenium deficiency on principal indexes of chicken kidney function. Biol. Trace Elem. Res. 2015, 164, 58–63. [Google Scholar] [CrossRef] [PubMed]
  120. Neeff, D.V.; Ledoux, D.R.; Rottinghaus, G.E.; Bermudez, A.J.; Dakovic, A.; Murarolli, R.A.; Oliveira, C.A.F. In vitro and in vivo efficacy of a hydrated sodium calcium aluminosilicate to bind and reduce aflatoxin residues in tissues of broiler chicks fed aflatoxin B1. Poult. Sci. 2013, 92, 131–137. [Google Scholar] [CrossRef] [PubMed]
  121. Özen, H.; Karaman, M.; Çiğremiş, Y.; Tuzcu, M.; Özcan, K.; Erdağ, D. Effectiveness of melatonin on aflatoxicosis in chicks. Res. Vet. Sci. 2009, 86, 485–489. [Google Scholar] [CrossRef] [PubMed]
  122. Uyar, A.; Yener, Z.; Dogan, A. Protective effects of Urtica dioica seed extract in aflatoxicosis: Histopathological and biochemical findings. Br. Poult. Sci. 2016, 57, 235–245. [Google Scholar] [CrossRef] [PubMed]
  123. Yu, Z.; Wang, F.; Liang, N.; Wang, C.; Peng, X.; Fang, J.; Cui, H.; Mughal, M.J.; Lai, W. Effect of selenium supplementation on apoptosis and cell cycle blockage of renal cells in broilers fed a diet containing aflatoxin B1. Biol. Trace Elem. Res. 2015, 168, 242–251. [Google Scholar] [CrossRef] [PubMed]
  124. Liang, N.; Wang, F.; Peng, X.; Fang, J.; Cui, H.; Chen, Z.; Lai, W.; Zhou, Y.; Geng, Y. Effect of sodium selenite on pathological changes and renal functions in broilers fed a diet containing aflatoxin B1. Int. J. Environ. Res. Public Health 2015, 12, 11196–11208. [Google Scholar] [CrossRef]
  125. Karaman, M.; Basmacioglu, H.; Ortatatli, M.; Oguz, H. Evaluation of the detoxifying effect of yeast glucomannan on aflatoxicosis in broilers as assessed by gross examination and histopathology. Br. Poult. Sci. 2005, 46, 394–400. [Google Scholar] [CrossRef] [PubMed]
  126. Huang, Q.; Gao, X.; Liu, P.; Lin, H.; Liu, W.; Liu, G.; Zhang, J.; Deng, G.; Zhang, C.; Cao, H.; et al. The relationship between liver-kidney impairment and viral load after nephropathogenic infectious bronchitis virus infection in embryonic chickens. Poult. Sci. 2017, 96, 1589–1597. [Google Scholar] [CrossRef] [PubMed]
  127. Chen, N.N.; Liu, B.; Xiong, P.W.; Guo, Y.; He, J.N.; Hou, C.C.; Ma, L.X.; Yu, D.Y. Safety evaluation of zinc methionine in laying hens: Effects on laying performance, clinical blood parameters, organ development, and histopathology. Poult. Sci. 2018, 97, 1120–1126. [Google Scholar] [CrossRef] [PubMed][Green Version]
  128. Ortatatli, M.; Ciftci, M.K.; Tuzcu, M.; Kaya, A. The effects of aflatoxin on the reproductive system of roosters. Res. Vet. Sci. 2002, 72, 29–36. [Google Scholar] [CrossRef] [PubMed]
  129. Bagherzadeh Kasmani, F.; Torshizi, K.; Mehri, M. Effect of Brevibacillus laterosporus Probiotic on Hematology, Internal Organs, Meat Peroxidation and Ileal Microflora in Japanese Quails Fed Aflatoxin B1. J. Agric. Sci. Technol. 2018, 20, 459–468. [Google Scholar]
  130. Eraslan, G.; Akdoğan, M.; LİMAN, B.C.; Kanbur, M.; DELİBAŞ, N. Effects of dietary aflatoxin and hydrate sodium calcium aluminosilicate on triiodothyronine, thyroxine, thyrotrophin and testosterone levels in quails. Turk. J. Vet. Anim. Sci. 2006, 30, 41–45. [Google Scholar]
  131. Doerr, J.A.; Ottinger, M.A. Delayed reproductive development resulting from aflatoxicosis in juvenile Japanese quail. Poult. Sci. 1980, 59, 1995–2001. [Google Scholar] [CrossRef] [PubMed]
  132. Wolzak, A.; Pearson, A.M.; Coleman, T.H.; Pestka, J.J.; Gray, J.I.; Chen, C. Aflatoxin carryover and clearance from tissues of laying hens. Food Chem. Toxicol. 1986, 24, 37–41. [Google Scholar] [CrossRef]
  133. European Commission. Commission Directive (EU) No 2003/100/EC of 31 October 2003 amending Annex I to Directive 2002/32/EC of the European Parliament and of the Council on undesirable substances in animal feed. Off. J. Eur. Union 2003, L285/33–L285/37. [Google Scholar]
  134. Oguz, H.; Kurtoglu, V. Effect of clinoptilolite on performance of broiler chickens during experimental aflatoxicosis. Br. Poult. Sci. 2000, 41, 512–517. [Google Scholar] [CrossRef] [PubMed]
  135. Chen, X.; Horn, N.; Applegate, T.J. Efficiency of hydrated sodium calcium aluminosilicate to ameliorate the adverse effects of graded levels of aflatoxin B1 in broiler chicks. Poult. Sci. 2014, 93, 2037–2047. [Google Scholar] [CrossRef]
  136. Bhatti, S.A.; Khan, M.Z.; Hassan, Z.U.; Saleemi, M.K.; Saqib, M.; Khatoon, A.; Akhter, M. Comparative efficacy of Bentonite clay, activated charcoal and Trichosporon mycotoxinivorans in regulating the feed-to-tissue transfer of mycotoxins. J. Sci. Food Agric. 2018, 98, 884–890. [Google Scholar] [CrossRef]
  137. Lala, A.O.; Oso, A.O.; Ajao, A.M.; Idowu, O.M.; Oni, O.O. Effect of supplementation with molecular or nano-clay adsorbent on growth performance and haematological indices of starter and grower turkeys fed diets contaminated with varying dosages of aflatoxin B1. Livest. Sci. 2015, 178, 209–215. [Google Scholar] [CrossRef]
  138. Lala, A.O.; Ajayi, O.L.; Oso, A.O.; Ajao, M.O.; Oni, O.O.; Okwelum, N.; Idowu, O.M.O. Effect of dietary supplementation with clay-based binders on biochemical and histopathological changes in organs of turkey fed with aflatoxin-contaminated diets. J. Anim. Physiol. Anim. Nutr. 2016, 100, 1191–1202. [Google Scholar] [CrossRef] [PubMed]
  139. Shetty, P.H.; Jespersen, L. Saccharomyces cerevisiae and lactic acid bacteria as potential mycotoxin decontaminating agents. Trends Food. Sci Technol. 2006, 17, 48–55. [Google Scholar] [CrossRef]
  140. Magnoli, A.P.; Rodriguez, M.C.; Pereyra, M.G.; Poloni, V.L.; Peralta, M.F.; Nilson, A.J.; Miazzo, R.D.; Bagnis, G.; Chiacchiera, S.M.; Cavaglieri, L.R. Use of yeast (Pichia kudriavzevii) as a novel feed additive to ameliorate the effects of aflatoxin B1 on broiler chicken performance. Mycotoxin Res. 2017, 33, 273–283. [Google Scholar] [CrossRef] [PubMed]
  141. Pizzolitto, R.P.; Armando, M.R.; Salvano, M.A.; Dalcero, A.M.; Rosa, C.A. Evaluation of Saccharomyces cerevisiae as an antiaflatoxicogenic agent in broiler feedstuffs. Poult. Sci. 2013, 92, 1655–1663. [Google Scholar] [CrossRef]
  142. Bovo, F.; Franco, L.T.; Kobashigawa, E.; Rottinghaus, G.E.; Ledoux, D.R.; Oliveira, C.A.F. Efficacy of beer fermentation residue containing Saccharomyces cerevisiae cells for ameliorating aflatoxicosis in broilers. Poult. Sci. 2015, 94, 934–942. [Google Scholar] [CrossRef] [PubMed]
  143. Fan, Y.; Zhao, L.; Ma, Q.; Li, X.; Shi, H.; Zhou, T.; Zhang, J.; Ji, C. Effects of Bacillus subtilis ANSB060 on growth performance, meat quality and aflatoxin residues in broilers fed moldy peanut meal naturally contaminated with aflatoxins. Food Chem. Toxicol. 2013, 59, 748–753. [Google Scholar] [CrossRef] [PubMed]
  144. Fan, Y.; Zhao, L.; Ji, C.; Li, X.; Jia, R.; Xi, L.; Zhang, J.; Ma, Q. Protective effects of bacillus subtilis ansb060 on serum biochemistry, histopathological changes and antioxidant enzyme activities of broilers fed moldy peanut meal naturally contaminated with aflatoxins. Toxins 2015, 7, 3330–3343. [Google Scholar] [CrossRef] [PubMed]
  145. Jia, R.; Ma, Q.; Fan, Y.; Ji, C.; Zhang, J.; Liu, T.; Zhao, L. The toxic effects of combined aflatoxins and zearalenone in naturally contaminated diets on laying performance, egg quality and mycotoxins residues in eggs of layers and the protective effect of Bacillus subtilis biodegradation product. Food Chem. Toxicol. 2016, 90, 142–150. [Google Scholar] [CrossRef] [PubMed]
  146. Khanian, M.; Karimi-Torshizi, M.A.; Allameh, A. Alleviation of aflatoxin-related oxidative damage to liver and improvement of growth performance in broiler chickens consumed Lactobacillus plantarum 299v for entire growth period. Toxicon 2019, 158, 57–62. [Google Scholar] [CrossRef] [PubMed]
  147. Chen, K.; Fang, J.; Peng, X.; Cui, H.; Chen, J.; Wang, F.; Chen, Z.; Zuo, Z.; Deng, J.; Lai, W.; et al. Effect of selenium supplementation on aflatoxin B1-induced histopathological lesions and apoptosis in bursa of Fabricius in broilers. Food Chem. Toxicol. 2014, 74, 91–97. [Google Scholar] [CrossRef] [PubMed]
  148. Chen, K.; Peng, X.; Fang, J.; Cui, H.; Zuo, Z.; Deng, J.; Chen, Z.; Geng, Y.; Lai, W.; Tang, L.; et al. Effects of dietary selenium on histopathological changes and T cells of spleen in broilers exposed to aflatoxin B1. Int. J. Environ. Res. Public Health 2014, 11, 1904–1913. [Google Scholar] [CrossRef] [PubMed]
  149. Hu, P.; Zuo, Z.; Wang, F.; Peng, X.; Guan, K.; Li, H.; Fang, J.; Cui, H.; Su, G.; Ouyang, P.; et al. The Protective Role of Selenium in AFB1-Induced Tissue Damage and Cell Cycle Arrest in Chicken’s Bursa of Fabricius. Biol. Trace Elem. Res. 2018, 185, 486–496. [Google Scholar] [CrossRef] [PubMed]
  150. Fang, J.; Zhu, P.; Yang, Z.; Peng, X.; Zuo, Z.; Cui, H.; Ouyang, P.; Shu, G.; Chen, Z.; Huang, C.; et al. Selenium Ameliorates AFB1-Induced Excess Apoptosis in Chicken Splenocytes Through Death Receptor and Endoplasmic Reticulum Pathways. Biol. Trace Elem. Res. 2018, 187, 273–283. [Google Scholar] [CrossRef]
  151. Li, Y.; Ma, Q.G.; Zhao, L.H.; Wei, H.; Duan, G.X.; Zhang, J.Y.; Ji, C. Effects of lipoic acid on immune function, the antioxidant defense system, and inflammation-related genes expression of broiler chickens fed aflatoxin contaminated diets. Int. J. Mol. Sci. 2014, 15, 5649–5662. [Google Scholar] [CrossRef] [PubMed]
  152. Zhang, N.Y.; Qi, M.; Zhao, L.; Zhu, M.K.; Guo, J.; Liu, J.; Gu, C.Q.; Rajput, S.A.; Krumm, C.S.; Qi, D.S.; et al. Curcumin prevents aflatoxin B1 hepatoxicity by inhibition of cytochrome P450 isozymes in chick liver. Toxins 2016, 8, 327. [Google Scholar] [CrossRef] [PubMed]
  153. Sun, L.H.; Zhang, N.Y.; Zhu, M.K.; Zhao, L.; Zhou, J.C.; Qi, D.S. Prevention of Aflatoxin B1 Hepatoxicity by Dietary Selenium Is Associated with Inhibition of Cytochrome P450 Isozymes and Up-Regulation of 6 Selenoprotein Genes in Chick Liver3. J. Nutr. 2016, 146, 655–661. [Google Scholar] [CrossRef] [PubMed]
  154. Gowda, N.K.S.; Ledoux, D.R.; Rottinghaus, G.E.; Bermudez, A.J.; Chen, Y.C. Efficacy of turmeric (Curcuma longa), containing a known level of curcumin, and a hydrated sodium calcium aluminosilicate to ameliorate the adverse effects of aflatoxin in broiler chicks. Poult. Sci. 2008, 87, 1125–1130. [Google Scholar] [CrossRef] [PubMed]
Figure 1. Impacts of aflatoxin B1 (AFB1) on poultry organs functions, productivity, and consumer health, and nutritional factors that might mitigate these impacts. The presence of AFB1 in the diet of poultry leads to body organs with abnormal sizes, stimulates the production of cytochrome P450 isoenzymes to convert AFB1 into AFB1-8,9-expoxide (AFBO; as the more toxic form of AFB1), oxidative damage, and organ malfunctions, which led to low productivity, decreased reproductive performance, high susceptibility to diseases, and the accumulation of AFB1 in eggs and meat, which can be harmful to the health of consumers. Adding inorganic AFB1 binders can bind AFB1 and reducing the accumulation of AFB1 in eggs and meat according to their efficiency. Organic AFB1 binders, such as probiotics, can bind or absorb AFB1 to decrease the conversion of AFB1 into AFBO by suppressing cytochrome P450 isoenzymes, as well as alleviating oxidative damage to organs and reducing the accumulation of AFB1 in eggs and meat. The addition of antioxidants, such as selenium and curcumin, can decrease the conversion of AFB1 into AFBO by suppressing cytochrome P450 isoenzymes and alleviate oxidative damage to organs.
Figure 1. Impacts of aflatoxin B1 (AFB1) on poultry organs functions, productivity, and consumer health, and nutritional factors that might mitigate these impacts. The presence of AFB1 in the diet of poultry leads to body organs with abnormal sizes, stimulates the production of cytochrome P450 isoenzymes to convert AFB1 into AFB1-8,9-expoxide (AFBO; as the more toxic form of AFB1), oxidative damage, and organ malfunctions, which led to low productivity, decreased reproductive performance, high susceptibility to diseases, and the accumulation of AFB1 in eggs and meat, which can be harmful to the health of consumers. Adding inorganic AFB1 binders can bind AFB1 and reducing the accumulation of AFB1 in eggs and meat according to their efficiency. Organic AFB1 binders, such as probiotics, can bind or absorb AFB1 to decrease the conversion of AFB1 into AFBO by suppressing cytochrome P450 isoenzymes, as well as alleviating oxidative damage to organs and reducing the accumulation of AFB1 in eggs and meat. The addition of antioxidants, such as selenium and curcumin, can decrease the conversion of AFB1 into AFBO by suppressing cytochrome P450 isoenzymes and alleviate oxidative damage to organs.
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Table 1. Reported levels of aflatoxin B1 that impair poultry productivity.
Table 1. Reported levels of aflatoxin B1 that impair poultry productivity.
BirdAflatoxin Dose *Fungal StrainReference
Chickens2000A. parasiticus (NRLL 2999)[31]
Chickens22A. parasiticus (FRR 2999)[29]
Chickens2A. parasiticus (PTCC 5286)[43,44]
Chickens1000A. flavus (NRRL 3357)[30]
Chickens250A. flavus (KP137700)[28]
Chickens40A. flavus (Chinese isolate)[45]
Laying hens2500A. parasiticus (SRRC 148)[9]
Laying hens500A. parasiticus (ATCC 15517)[24]
Breeder hens3000A. parasiticus (NRRL 2999)[32]
Breeder hens500A. flavus (NRRL 6540; CECT 2687)[46]
Quail2500A. parasiticus (PTCC 5286)[47,48]
Quail1500A. parasiticus (NRRL 2999)[33,34]
Quail500A. flavus[49]
Ducks1100A. parasiticus (NRRL 2999)[35]
Ducks20A. flavus (CICC 2219)[50]
Turkeys 500A. parasiticus (NRRL 2999)[36,37]
* Aflatoxin dose (μg /kg).
Table 2. Harmful effects of aflatoxin B1 on immune organs in poultry.
Table 2. Harmful effects of aflatoxin B1 on immune organs in poultry.
BirdAflatoxin Dose (μg/kg)Fungal StrainRelative Weights of OrgansReference
SpleenBursaThymus
Chickens40A. flavus (Chinese isolate)+[25]
Chickens22A. parasiticus (FRR 2999)+±ND[29]
Chickens4000A. parasiticus (NRRL 2999)+NDND[83]
Offspring of breeder hens5000A. flavus (NRRL 6540 CECT 2687)±[80]
Turkeys330A. flavus (UNIGRAS 1231)±±ND[71]
Turkeys500A. parasiticus (NRRL 2999)±±ND[37]
Abbreviations: + increase; − decrease; ± no effect; ND, not determined.
Table 3. Harmful effects of aflatoxin B1 on liver in poultry.
Table 3. Harmful effects of aflatoxin B1 on liver in poultry.
BirdAflatoxin Dose (μg/kg)Fungal StrainRelative Weight of LiverReference
Chickens40A. flavus (Chinese isolate)+[25]
Chickens250A. flavus (KP137700)+[28]
Chickens1000A. flavus (NRRL 3357)+[30]
Ducks20A. flavus (CICC 2219)+[50]
Ducks1100A. parasiticus (NRRL 2999)±[35]
Turkeys330A. flavus (UNIGRAS 1231)[71]
Turkeys500A. parasiticus (NRRL 2999)+[37]
Laying hens500A. parasiticus (ATCC 15517)+[24]
Laying hens1000A. parasiticus+[107]
Laying hens2500A. parasiticus (SRRC 148)+[9]
Quail2500A. parasiticus (PTCC 5286)+[48]
Abbreviations: + increase; − decrease; ± no effect.
Table 4. Some additives used in poultry diets to counteract the toxicity of aflatoxin B1.
Table 4. Some additives used in poultry diets to counteract the toxicity of aflatoxin B1.
ItemAmount (g/kg) Aflatoxin Dose (μg/kg)BirdReference
Clinoptilolite15.02500 (A. parasiticus NRRL 2999)chickens[134]
Hydrated sodium calcium aluminosilicate5.02000 (A. parasiticus NRRL 2999)chickens[135]
Hydrated sodium calcium aluminosilicate3.040 (A. flavus)chickens[25]
Bentonite7.52000 (A. parasiticus NRRL 2999)chickens[70]
Bentonite7.5600 (A. flavus NRRL 6540; CECT 2687)chickens[136]
Nano-composite magnetic graphene oxide with chitosan5.022 (A. parasiticus FRR 2999)chickens[29]
Yeast cell walls 11.5350 (naturally contaminated)chickens[72]
Yeast 21.0100 (A. parasiticus NRRL 2999)chickens[140]
Probiotic 3 1.0250 (A.flavus KP137700)chickens[28]
Probiotic 4 2.070 (naturally contaminated)chickens[143,144]
Probiotic 5 1.022 (naturally contaminated)ducks[56]
Probiotic 61.0123 (naturally contaminated)hens[145]
Alpha-lipoic acid300 a300 (A. parasiticus NRRL 2999)chickens[77]
Urtica diocia seed extract300 b1000 (A. parasiticus NRRL 2999)chickens[122]
Grape seed proanthocyanidin extract250 a1000 (A. flavus NRRL 3357)chickens[30]
Curcuminoids74.0 a1000 (A. parasiticus NRRL 2999)chickens[154]
Yeast wall cells 1 (Saccharomyces cerevisiae); Yeast 2 (Pichia kudriavzevii); Probiotic 3 (commercial product); Probiotic 4 (Bacillus subtilis ANSB060); Probiotic 5 (Bacillus subtilis ANSB060); Probioti c6 (Bacillus subtilis ANSB060 and Bacillus subtilis ANSB01G). a (mg/kg); b (mL/kg).

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