Search Results (8)

Mycotoxin contamination in maize poses significant food and feed safety risks, particularly in regions with variable climatic conditions like Serbia. This study investigated the occurrence of regulated mycotoxins in maize harvested across the Republic of Serbia from 2021 to 2023, emphasizing the impact of climatic factors. A total of 548 samples of unprocessed maize grains were analysed for the presence of key mycotoxins, including aflatoxins, ochratoxin A, zearalenone, deoxynivalenol, fumonisins, and trichothecenes type A (T-2 and HT-2 toxins), using validated analytical methods. The results revealed high contamination frequencies, with aflatoxins and fumonisins being the most prevalent. The results revealed substantial temporal variability and frequent co-contamination of mycotoxins. Aflatoxin B₁ (AFB₁) was the most concerning contaminant, with 73.2% of the samples in 2022 exceeding the European regulatory limit for human consumption (5 µg/kg) for un processed maize grains, reaching peak concentrations of 527 µg/kg, which is 105.4 times higher than the allowed limit. For animal feed, the limit of 20 µg/kg was exceeded in 40.5% of the samples, with the highest concentration being 26.4 times greater than the maximum allowable level. In 2021, the non-compliance rates for AFB₁ in food and feed were 8.3% and 2.3%, respectively, while in 2023, they were 23.2% and 12.2%, respectively. Fumonisins contamination was also high, particularly in 2021, with fumonisin B₁ (FB₁) detected in 87.1% of samples and average concentrations reaching 4532 µg/kg. Although levels decreased in 2023 (70.7% occurrence, average 885 µg/kg), contamination remained significant. Deoxynivalenol (DON) contamination was consistently high (>70% of samples), with peak concentrations of 606 µg/kg recorded in 2021. Zearalenone (ZEN) and ochratoxin A (OTA) occurred less frequently, but ZEN levels peaked in 2022 at 357.6 µg/kg, which is above the regulatory limit of 350 µg/kg for food. Trichothecenes (HT-2 and T-2 toxins) were detected sporadically, with concentrations well below critical thresholds. Co-occurrence of mycotoxins was frequent, with significant mixtures detected, particularly between aflatoxins and fumonisins, as well as other fusarial toxins. The analysis demonstrated that temperature, humidity, and rainfall during both the growing and harvest seasons strongly influenced mycotoxin levels, with the most severe contamination occurring under specific climatic conditions. Notably, the highest mycotoxin levels, like aflatoxins, were linked to warmer temperatures and lower rainfall. The high non-compliance rates for aflatoxins and fumonisins and co-contamination pose significant food and feed safety risks. From a public health perspective, chronic exposure to contaminated maize increases the likelihood of carcinogenesis and reproductive disorders. Reduced productivity and bioaccumulation in animal tissues/products represent serious economic and safety concerns for livestock. This study provides insights into the potential risks to food and feed safety and the need for enhanced regulatory frameworks, continuous monitoring, and mitigation strategies in Serbia as well as other geographical regions. Full article

Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research. Full article

In the context of the mysterious Balkan endemic nephropathy of the 1900s, and the discovery in the 1960s of the potent mycotoxin ochratoxin A, experimental research projects sought to explore any inter-relationship. Experimental lifetime administration of the toxin to male rats had revealed renal DNA adducts with the toxin, correlated with renal tumours, confirmation of which required molecular evidence. Consequently, production of ¹⁴C-ochratoxin A of a high specific radioactivity was required, practical biosynthetic detail of which had not previously been published. A fermentation study of Aspergillus ochraceous was carried out during 2002 for a European project, to select for the production of high-quality ¹⁴C-ochratoxin A, necessarily exploring for the maximum diversion of ¹⁴C-sodium acetate into the pentaketide portion of mycotoxin. Experimentation necessarily had to optimise the competitive context of fungal growth dynamics and addition of the biosynthetic precursor in the early days of shaken-flask fermentation before adding the radiolabelled precursor. From optimal fermentation, 50 mg of the ¹⁴C ochratoxin A was supplied within a European project for DNA adduct experimentation, but that proved negative as subsequently published. Experimental description of the radiolabelled ochratoxin A production was later made in a doctoral thesis, but is first publicised here. Further review of the literature reveals an explanation for the published failure to confirm rat DNA/ochratoxin A adduct formation, for which further experimentation is now recommended. Full article

Ochratoxin A (OTA) is a common secondary metabolite of Aspergillus ochraceus, A. carbonarius, and Penicillium verrucosum. This mycotoxin is largely present as a contaminant in several cereal crops and human foodstuffs, including grapes, corn, nuts, and figs, among others. Preclinical studies have reported the involvement of OTA in metabolic, physiologic, and immunologic disturbances as well as in carcinogenesis. More recently, it has also been suggested that OTA may impair hippocampal neurogenesis in vivo and that this might be associated with learning and memory deficits. Furthermore, aside from its widely proven toxicity in tissues other than the brain, there is reason to believe that OTA contributes to neurodegenerative disorders. Thus, in this present in vivo study, we investigated this possibility by intraperitoneally (i.p.) administering 3.5 mg OTA/kg body weight to adult male mice to assess whether chronic exposure to this mycotoxin negatively affects cell viability in the dentate gyrus of the hippocampus. Immunohistochemistry assays showed that doses of 3.5 mg/kg caused a significant and dose-dependent reduction in repetitive cell division and branching (from 12% to 62%). Moreover, the number of countable astrocytes (p < 0.001), young neurons (p < 0.001), and mature neurons (p < 0.001) negatively correlated with the number of i.p. OTA injections administered (one, two, three, or six repeated doses). Our results show that OTA induced adverse effects in the hippocampus cells of adult mice brain tissue when administered in cumulative doses. Full article

Mammalian animal toxicity of ochratoxin A (OTA) has focused largely in the past half-century on pigs because of initial recognition of it as a principal cause of intermittent growth suppression and renal disease caused by mouldy feed. Subsequent classical toxicology has used laboratory rodents because renal pathology in pigs raised questions concerning possible involvement in the human idiopathic bilateral renal atrophy of Balkan endemic nephropathy for which OTA was a focus of attention for human nephropathy through 1980s and into 2000s. Emphasis on human nephropathy has more recently concerned the plant metabolite aristolochic acid. Recognition that agricultural management can often minimise food and feed-stuff spoilage by OTA-producing Aspergilli and Penicillia has moderated some of the risks for animals. Legislation for human food safety combined with sophisticated analysis generally provides safety in the developed world. Chronic experimental exposure of male rats, in the absence of clinical dis-ease, specifically causes renal cancer. The possibility of this as a unique model for the human has generated considerable experimental evidence which may be more directly relevant for carcinogenesis in the complex kidney than that obtained from biochemical toxicities in vitro. Nevertheless, there does not appear to be any case of human renal or urinary tract cancer for which there is verified etiological proof for causation by OTA, contrary to much claim in the literature. To contribute to such debate, histopathology review of OTA/rat renal cancers, augmented where appropriate by immune profiles, has been completed for all remaining tumours in our research archive. Overall consistency of positivity for vimentin, is matched with occasional positives either for CD10 or the cytokeratin MNF 116. The current situation is discussed. Suggestion that OTA could cause human testicular cancer has also been challenged as unsupported by any experimental findings in rats, where the Leydig cell tumour immune profile does not match that of human germ cell neoplasms. Full article

Ochratoxin A (OTA) is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis. Full article

Mycotoxins are produced mainly by the mycelial structure of filamentous fungi, or more specifically, molds. These secondary metabolites are synthesized during the end of the exponential growth phase and appear to have no biochemical significance in fungal growth and development. The contamination of foods and feeds with mycotoxins is a significant problem for the adverse effects on humans, animals, and crops that result in illnesses and economic losses. The toxic effect of the ingestion of mycotoxins in humans and animals depends on a number of factors including intake levels, duration of exposure, toxin species, mechanisms of action, metabolism, and defense mechanisms. In general, the consumption of contaminated food and feed with mycotoxin induces to neurotoxic, immunosuppressive, teratogenic, mutagenic, and carcinogenic effect in humans and/or animals. The most significant mycotoxins in terms of public health and agronomic perspective include the aflatoxins, ochratoxin A (OTA), trichothecenes, fumonisins, patulin, and the ergot alkaloids. Due to the detrimental effects of these mycotoxins, several strategies have been developed in order to reduce the risk of exposure. These include the degradation, destruction, inactivation or removal of mycotoxins through chemical, physical and biological methods. However, the results obtained with these methods have not been optimal, because they may change the organoleptic characteristics and nutritional values of food. Another alternative strategy to prevent or reduce the toxic effects of mycotoxins is by applying antimutagenic agents. These substances act according to several extra- or intracellular mechanisms, their main goal being to avoid the interaction of mycotoxins with DNA; as a consequence of their action, these agents would inhibit mutagenesis and carcinogenesis. This article reviews the main strategies used to control AFB₁ and ochratoxin A and contains an analysis of some antigenotoxic substances that reduce the DNA damage caused by these mycotoxins. Full article

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours. Full article