Search Results (324)

T-2 toxin and HT-2 toxin are commonly found in agricultural products and animal feed, posing serious effects to both humans and animals. This study employed combination index (CI) modeling and metabolomics to assess the combined cytotoxic effects of T-2 and HT-2 on four porcine cell types: intestinal porcine epithelial cells (IPEC-J2), porcine Leydig cells (PLCs), porcine ear fibroblasts (PEFs), and porcine hepatocytes (PHs). Cell viability assays revealed a dose-dependent reduction in viability across all cell lines, with relative sensitivities in the order: IPEC-J2 > PLCs > PEFs > PHs. Synergistic cytotoxicity was observed at low concentrations, while antagonistic interactions emerged at higher doses. Untargeted metabolomic profiling identified consistent and significant metabolic perturbations in four different porcine cell lines under co-exposure conditions. Notably, combined treatment with T-2 and HT-2 resulted in a uniform downregulation of LysoPC (22:6), LysoPC (20:5), and LysoPC (20:4), implicating disruption of membrane phospholipid integrity. Additionally, glycerophospholipid metabolism was the most significantly affected pathway across all cell lines. Ether lipid metabolism was markedly altered in PLCs and PEFs, whereas PHs displayed a unique metabolic response characterized by dysregulation of tryptophan metabolism. This study identified markers of synergistic toxicity and common alterations in metabolic pathways across four homologous porcine cell types under the combined exposure to T-2 and HT-2 toxins. These findings enhance the current understanding of the molecular mechanisms underlying mycotoxin-induced the synergistic toxicity. Full article

Zearalenone (ZEN), a mycotoxin commonly present in maize-based feed, poses a health risk to dairy cows. While the hepatic effects of ZEN are increasingly studied, little is known about its impact on cows with altered energy metabolism. This study investigated the transcriptional response of liver cells isolated from healthy and ketotic cows to ZEN exposure using a novel in vitro model. Hepatocytes were obtained via biopsy from 12 cows, cultured under standardized conditions, and exposed to ZEN (0–100 µM) for 1, 3, and 6 h. Gene expression analysis focused on targets related to glucose and lipid metabolism. ZEN induced time- and dose-dependent changes in gene expression, with the most prominent effects observed after 1 h. Key metabolic genes were differentially regulated depending on the cow’s metabolic status. Notably, hepatocytes from healthy cows showed a stronger transcriptional response than those from ketotic cows, indicating reduced metabolic adaptability in energy-compromised animals. Significant interaction effects between ZEN dose and metabolic status were observed, especially for genes involved in glycolysis and fatty acid metabolism. This study presents a novel in vitro model and emphasizes the need to consider metabolic health when assessing the risks of mycotoxin exposure in dairy cattle. Full article

Resorcylic acid lactones (RALs) are fungal metabolites with known biological activity. Zeranol, a synthetic RAL, has been used as an estrogenic growth promoter in cattle; however, its use is prohibited in several countries. Zearalenone, a mycotoxin produced by Fusarium spp., is commonly found in contaminated animal feed and can be metabolized into other RALs, which are subsequently excreted in urine. To differentiate between natural contamination from feed and the illegal administration of zeranol, the European Union Reference Laboratory for Growth Promoters (EURL) developed a mathematical equation. This study aims to evaluate the detection and quantification of RALs in bovine urine from animals fed zearalenone-contaminated diets, implanted with zeranol, or subjected to both conditions. RALs were detected and quantified in the urine of cattle consuming contaminated corn, while zeranol and taleranol were identified in the urine of implanted animals. The EURL equation proved to be a valuable tool for determining the origin of RALs in bovine urine and holds significant potential for monitoring and enforcing regulations regarding the illegal use of zeranol. Full article

Patulin (PAT) is a mycotoxin commonly found in fruits and contaminated feedstuffs, known for its gastrointestinal and systemic toxicity. However, the mechanisms underlying PAT-induced damage to intestinal epithelial cells remain poorly understood. In this study, we demonstrated that 6.5 µM PAT exposure for 24 h reduced glutamine (GLN) uptake and altered the expression of GLN transporters and related metabolic enzymes in IPEC-J2 cells. This concentration was selected based on previous in vitro studies that reported PAT-induced cytotoxicity in porcine intestinal epithelial cells. Moreover, PAT also upregulated ER stress markers (DDIT3, EIF2AK3, ERN1, and HSPA5) and inflammatory cytokines (IL-8, IL-1β, and TNF-α), while decreasing ZO-1 localization, indicating disrupted epithelial barrier integrity. Although 6 mM GLN supplementation only partially mediated ER stress and inflammatory responses, it more effectively restored ZO-1 localization. A high-throughput screening of 324 natural products was conducted to identify potential protective agents, identifying Nymphoides peltata extract as a promising candidate. Co-treatment with 80 ng/μL N. peltata extract improved GLN uptake, partially alleviated ER stress and inflammation, and significantly restored tight junction structure in PAT-exposed cells. Collectively, these findings suggest that N. peltata could serve as a novel natural therapeutic for enhancing intestinal resilience against PAT-induced toxicity. Specifically, this study highlights the potential use of N. peltata extract as a natural feed additive to protect intestinal health in livestock under mycotoxin stress. Full article

As a typical agricultural waste, the resource utilization of corn stover (CS) plays a crucial role in the coordinated optimization of ecological and economic benefits. In order to enhance the utilization of CS resources, Lentilactobacillus (L.) buchneri (LB) and different proportions of Artemisia argyi (AA) were added to CS to investigate the impact of additives on the fermentation quality and aerobic stability of corn stover silage (CSS). This study revealed that the separate addition of AA or LB in CS effectively improved the silage quality and aerobic stability. Specifically, LB exhibited the lowest pH value of 3.72 at 90 d of fermentation, while the NH₃-N content was 0.07 g/kg DM during the anaerobic fermentation stage and 0.19 g/kg DM during the aerobic exposure stage (p < 0.05). Mixing 30% AA increased the lactic acid content, lowered the pH, maintained a higher relative abundance of Lactobacillus, and reduced mycotoxin levels. In terms of aerobic stability, all AA-treated groups demonstrated superior performance compared to the LB treatment. Additionally, it was observed, that in the 30% AA group, Candida exhibited the highest relative abundance. Importantly, the addition of AA upregulated carbohydrate metabolism and lipid metabolism during the ensiling process, and their relative abundances remained high during aerobic exposure. Fully utilizing CS resources as feed to provide fiber and nutrients for ruminants can not only reduce the pressure on forage demand but meet the development needs of “grain-saving” animal husbandry, which is conducive to solving the contradictions of “human–animal competition for food” and “human animal competition for land”. Full article

The replacement of ingredients from animal sources with plant-based ingredients is increasing the risk of contamination by mycotoxins in aquafeeds, potentially causing detrimental effects on fish welfare. However, limited research has been carried out so far on the impact of mycotoxins on fish health. Hence, the aim of this study was to assess the toxicological effects of the dietary emerging (enniatin B, ENNB) and regulated (fumonisin B1, FB1) mycotoxins (150 µg/kg) in different tissues of juvenile gilthead seabream (Sparus aurata) after 28 days of dietary exposure. Fitness indexes, plasma metabolites, and biomarkers of oxidative stress, metabolism, cellular, and neurotoxic damage were assessed. The exposure to each mycotoxin was sufficient to cause distinct effects in fish tissues. ENNB appears to be the most harmful mycotoxin to S. aurata, inducing changes on alkaline phosphatase and lipase activities in plasma, as well as protein and lipid degradation in liver. Increased lipid degradation was also induced in the brain by FB1 alone or combined with ENNB, whereas the exposure to the mixture inhibited acetylcholinesterase activity. Overall, this study contributes by highlighting the toxicological attributes of ENNB, thus reinforcing the need to include this mycotoxin in future legislation. Full article

Animal-based food is significant for human nutrition, as it represents an easily digestible source of high-quality proteins, fatty acids, fat-soluble vitamins, and energy. During evolution, humans developed anatomical, metabolic, and biochemical adaptations in the digestive tract, becoming increasingly dependent on nutritionally valuable food, such as animal-based products. Animal-based food can be a source of chemical substances that are harmful to health, such as contaminants (heavy metals, mycotoxins, organochlorine pesticides, etc.), veterinary drug residues, and additives. The subject of this paper is the determination of the content of essential (copper—Cu, iron—Fe, and chromium—Cr) and heavy and toxic metals (lead—Pb, cadmium—Cd, arsenic—As, and tin—Sn), as well as nitrites, in meat products, particularly pâtés and meat spreads available on the market in the Republic of Srpska. Determination of the content of metals was performed using the ICP-OES method, while nitrites were analyzed using the standard SRPS ISO 2918/1999 method. The obtained results indicate that the content of heavy and toxic metals and nitrites is lower than the maximum prescribed by national regulations, namely the Rulebook on Maximum Amounts of Certain Contaminants (Official Gazette of BA, No. 68/14, 79/16, 84/18) and the Rulebook on Additives in Food (Official Gazette of BA, No. 33/18 and 6/21). Full article

CYP1B1 is a key enzyme involved in xenobiotic and endogenous metabolism, yet its physiological role in bovine liver homeostasis remains unclear. In this study, we generated a CYP1B1 knockout (CYP1B1^KO) bovine hepatocyte-like cell line to indirectly investigate its role in liver function. Transcriptomic analysis revealed alterations in immune regulation, epithelial barrier integrity, and detoxification pathways, with concurrent compensatory CYP1A1 upregulation. Beyond its physiological role, CYP1B1 was found to actively participate in Aflatoxin B1 (AFB1) metabolism, a mycotoxin posing significant health risks to humans and livestock. Molecular docking suggested that CYP1B1 facilitates the conversion of AFB1 into AFM1 and AFBO. In agreement with these predictions, CYP1B1^KO cells exposed to AFB1 showed reduced AFM1 production and decreased cytotoxicity. Further transcriptomic analysis indicated that CYP1B1^KO cells exhibited mitigated oxidative stress and inflammatory responses, along with downregulation of CYP3A74, a key enzyme in AFB1 bioactivation. This suggests that CYP1B1 KO reduces AFB1 toxicity by directly limiting AFB1 bioactivation and indirectly modulating the broader hepatic CYP network, further limiting the formation of toxic intermediates. These findings provide novel insights into CYP1B1’s function in bovine hepatocytes, highlighting its dual role in maintaining liver homeostasis and mediating AFB1 metabolism. The observed interplay between CYP1B1, CYP1A1, and CYP3A74 underscores the complexity of AFB1 biotransformation and warrants further investigation into the coordinated regulation of xenobiotic metabolism in cattle. Full article

Fusarium verticillioides is a globally prevalent phytopathogenic fungus responsible for multiple diseases in maize and a major producer of the mycotoxin fumonisin B1 (FB1), a highly toxic fungal secondary metabolite (FSM). The histone code, which includes reversible modifications such as acetylation and methylation, plays a critical role in regulating chromatin structure and gene expression. In fungi, di- and tri-methylation of histone H3 at lysine 9 (H3K9me2/3) serves as a key epigenetic mark associated with heterochromatin formation and transcriptional repression. In this study, we identified and characterized a putative heterochromatin protein 1 (HP1) family member in F. verticillioides, designated FvHP1, based on conserved domain architecture and phylogenetic analyses. FvHP1 retains essential residues required for H3K9me2/3 recognition, supporting its functional conservation within the HP1 protein family. Phenotypic analysis of the ΔFvHP1 mutant revealed impaired vegetative growth, reduced conidiation and virulence, and altered FB1 mycotoxin production. Additionally, the accumulation of red pigment in the mutant was linked to the deregulation of secondary metabolism, specifically the overproduction of fusarubin-type naphthoquinones, such as 8-O-methylnectriafurone. These results support the role of FvHP1 in facultative heterochromatin-mediated repression of sub-telomeric biosynthetic gene clusters, including the pigment-associated PGL1 cluster. Our findings provide new insights into the epigenetic regulation of fungal pathogenicity and metabolite production, as well as the first evidence of a functional HP1 homolog in F. verticillioides. Full article

Radix astragali is a homologous plant of medicine and food with a variety of health benefits. However, our previous study showed that blue mold, caused by Penicillium polonicum, is the most important postharvest disease of fresh R. astragali during storage. Ozone, as a strong oxidizing agent, can effectively control the occurrence of postharvest diseases in fruits and vegetables. Nevertheless, there are few research studies on the effect of ozone-treated fresh Chinese traditional medicine. In this study, we investigated the effect of ozone gas on the postharvest blue mold development, mycotoxin accumulation, and main active component contents in fresh R. astragali infected by P. polonicum, and analyzed the possible action mechanism on ROS metabolism. The result indicates that ozone application significantly inhibited the development of postharvest blue mold caused by P. polonicum infection, reduced the disease incidence, disease index, and weight loss rate, maintained the main active ingredients in fresh R. astragali by activating ROS metabolism, enhanced the antioxidant enzymatic activity, thus avoiding oxidative damage caused by excessive ROS accumulation, and maintained the integrity of the cell membrane, ultimately controlling the occurrence of blue mold of R. astragali. Moreover, ozone treatment also maintained the contents of the main active ingredients in R. astragali before 14 d during P. polonicum infection. In addition, the amount of active ingredients of astragaloside I, calycosin-7-glucoside, and ononin in the ozone-treated group was higher than that in the control group during the storage period. We speculate that, under the action of ozone, astragaloside IV was converted into astragaloside II by oxidative modification and astragaloside II was further oxidized to astragaloside I, resulting in the accumulation of astragaloside I. Similarity, the hydrogen atoms (-H) on the benzene ring in formononetin were oxidized to phenolic hydroxyl groups (-OH) to generate calycosin, which was further converted into calycosin-7-glucoside, resulting in calycosin-7-glucoside accumulation. This study will provide the theoretical basis for ozone commercial application to control the occurrence of postharvest diseases of R. astragali. Full article

Fescue toxicosis (FT) is a mycotoxin-related disease caused by the ingestion of tall fescue, naturally infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. Some grazing on endophyte-free (E−) or non-toxic (NT), commercial endophyte-infected pastures takes place in the US as well. Earlier, we found that grazing on toxic fescue with low levels of EAs during fall affects thermoregulation, behavior, and weight gain. Building on these findings, the current study aimed to investigate how the presence of low EA-producing E+ or NT endophytes can influence animal metabolome, microbiome, and, ultimately, overall animal health. Eighteen Angus steers were placed on NT, E+, and E− fescue pastures for 28 days. Urine, rumen fluid (RF), rumen solid (RS), and feces were collected pre-exposure, and on days 2, 7, 14, 21, and 28. An untargeted high-resolution metabolomics approach was used to analyze urine and RF, while 16S rRNA-based next-generation sequencing (NGS) was used to examine RF, RS, feces, and fescue plant microbiomes. While alpha- or beta-microbiota diversity across all analyzed matrices were unaffected, there were specific effects of E+ on the relative abundance of some taxa (i.e., Prevotellaceae). Additionally, E+ grazing impacted aromatic amino acid metabolism in the urine and the metabolism of lipids in both the RF and urine. In both matrices, trace amine-related metabolic features differed markedly between E+ and the other groups. Compared to the endophyte-free group, endophyte presence, whether novel or toxic, influenced amino acid and carbohydrate metabolism, as well as unsaturated fatty acid biosynthesis. These findings suggest that low-EA-producing and non-toxic endophytes in fescue have more prominent effects on the metabolome than the microbiome, and this metabolome perturbation might be associated with decreased performance and reported physiological signs of FT. Full article

Ustilaginoidin D is a type of bis-naphtho-γ-pyrone mycotoxin produced by Ustilaginoidea virens, the causal agent of rice false smut. Although previous studies have demonstrated the inhibitory effect of ustilaginoidin D on ATP synthesis and cancer cell growth in mice, its specific health risks remain unclear. Here, we reveal that ustilaginoidin D is highly toxic to mice with an LD₅₀ value of 213 mg /kg·bw. Dose-dependent weight loss and liver damage were observed, accompanied by altered markers of liver cell damage, including the enzyme activities of alanine aminotransferase and aspartate aminotransferase and the content of glutathione in mouse liver. RNA-seq analysis of liver tissues from mice treated with 150 mg of ustilaginoidin D/kg·bw identified significant changes in gene expression profiles, with differentially expressed genes enriched in cancer-related pathways, hypertrophic cardiomyopathy, and metabolic pathways. RT-qPCR data are highly consistent with transcriptome analysis in expression profiles of 22 chemical-carcinogenesis-associated genes. These findings indicate that ustilaginoidin D induces acute toxicity and liver dysfunction in mice, raising serious concerns about its threat to human health. Full article

The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells were exposed to (A) mycotoxins, (B) the digesta of mycotoxin-contaminated bread formulated with P, or (C) bread enriched with FW + P. A proteomic approach using HPLC-MS/MS-QTOF was then employed to characterize the metabolic pathways affected by the presence of these components, as well as their ability to modulate the toxic effects exacerbated by mycotoxins. Gene ontology functional analysis revealed proteins primarily associated with nucleosome structure, such as the H3-H4 tetramer, H2A-H2B dimer, and HIRA, which were overexpressed in the presence of mycotoxins and, interestingly, downregulated with the addition of the functional ingredients. Additionally, important metabolic pathways associated with the RHO GTPase family, estrogen-dependent gene expression, and androgen receptor transcription stimulated by PKN1 activation were discovered. Network interaction analysis highlighted the modulation of cytoskeletal dynamics, cell migration, and stress responses. These findings provide novel insights into the neuroprotective potential of functional food components, supporting their use in mitigating mycotoxin-induced neuronal damage and opening new avenues for dietary-based neuroprotection strategies. Full article

This study reports on the whole genome sequencing of the hazelnut endophytic Fusarium isolate Hzn5 from Poland. It was identified as a member of the Fusarium citricola species complex based on a phylogenetic analysis which also pointed out that other hazelnut isolates, previously identified as F. lateritium and F. tricinctum, actually belong to this species complex. Genome annotation allowed the mapping of 4491 different protein sequences to the genome assembly. A further in silico search for their potential biosynthetic activity showed that predicted genes are involved in 1110 metabolic pathways. Moreover, the analysis of the genome sequence carried out in comparison to another isolate, previously identified as an agent of hazelnut gray necrosis in Italy, revealed a homology to several regions containing biosynthetic gene clusters for bioactive secondary metabolites. The resulting indications for the biosynthetic aptitude concerning some emerging mycotoxins, such as the enniatins and culmorin, should be taken into consideration with reference to the possible contamination of hazelnuts and derived products. Full article

Corn silage (CS) and high-moisture corn (HMC) represent fundamental ingredients in ruminant diets; however, their chemical complexity and susceptibility to mycotoxin contamination pose challenges for feed safety and quality assessment. This study applied an innovative approach combining untargeted metabolomics and mycotoxin profiling through ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS) to characterize the chemical profiles of CS (n = 19) and HMC (n = 13) samples collected from four farms in northern Italy over a period of two years. Fumonisin B1 (FB1) emerged as the most prevalent mycotoxin, with contamination levels significantly higher in HMC than CS, though all the detected levels complied with European Union (EU) guidance limits. Untargeted metabolomics distinguished CS and HMC based on their metabolic signatures: polyamines, amino acids, peptides, and phenolic acids typified CS, while HMC was primarily characterized by flavonoids and mycotoxins. Geographical origin significantly influenced both mycotoxin patterns and metabolite profiles, while the sampling season showed no significant impact. This study highlights the complementary value of metabolomics and mycotoxin screening to assess feed quality, identify biomarkers, and unravel the link between fungal contamination and biochemical composition, offering a robust strategy to support feed safety management in livestock production. Full article