Biological Action of Mycotoxins

Mycotoxins are ubiquitous, mold-produced toxins that contaminate a wide variety of foods and feeds. Ingestion of mycotoxins cause a range of toxic responses, from acute toxicity to long-term or chronic health disorders. Some mycotoxins have caused outbreaks of human toxicoses, and at least one mycotoxin, aflatoxin B1, is a presumed human hepatocarcinogen. As part of a comprehensive effort to curtail the adverse health effects posed by mycotoxins, substantial research has been conducted to determine the mechanism of action of mycotoxins in animals. This review presents some of the current knowledge on the biological action of four diverse classes of mycotoxins—aflatoxin B1, tricothecenes, zearalenone, and fumonisin B1—with particular emphasis on mechanisms of action

Aflatoxin mutagenesis and metabolism and their dietary modification in rainbow trout (Salmo gairdneri)

Aflatoxin B₁ (AFB₁) is a mold-produced toxin which has been shown to be a potent hepatocarcinogen in many animal species. Of the species studied thus far, rainbow trout have proven to be the most sensitive. Experiments were conducted to investigate various aspects of AFB₁ metabolism in this species, including in vitro mutagenesis, and effects of dietary modifiers of AFB, carcinogenesis on in vitro metabolism and mutagenesis. A comparative study of AFB₁ metabolism in two salmonid species was also conducted. In the first study, the relative mutagenic potencies of several alfatoxin metabolites were evaluated using a trout liver fraction system. Preliminary studies characterizing trout liver fractions for use as an activation system were described. The results from comparative mutagenicity experiments demonstrated that in vitro mutagenic potencies qualitatively correlated with the in vivo carcinogenic activities of various aflatoxins in rainbow trout. The importance of these findings is discussed. In the second study fish hepatocytes were characterized to examine possible differences in activation of AFB₁ to bacterial mutagens by hepatocytes from rainbow trout and coho salmon, two species which are known to differ markedly in sensitivity to the carcinogenic effects of AFB₁. Activation efficiency was approximately three times greater in hepatocytes from trout compared to salmon. A more marked difference was seen when S20 liver fractions from the two species were used. Analysis of unbound [³H]AFB₁ metabolites revealed that trout hepatocytes metabolized [³H]AFB₁ to a greater extent than salmon. The results accurately reflected in vivo carcinogenesis trends in salmonid fish. Additional experiments were conducted to evaluate the effects of dietary modifiers of AFB₁ carcinogenesis on in vitro mutagenesis and metabolism of AFB₁. Dietary β-naphthoflavone (β-NF) was shown to induce the production of a novel trout metabolite of AFB₁, aflatoxicol M₁ (AFL-M₁). AFL-M₁ exhibited a mutagenic potency less than AFB₁ or aflatoxicol (AFL), but greater than that of aflatoxin-M₁ (AFM₁). Dietary β-NF, however, appeared to have no effect on in vitro mutagenic activation of AFB₁ using hepatocytes or liver S20 fraction from trout. Dietary PCBs (Aroclor 1254) was shown to significantly decrease in vitro mutagenesis of AFB₁, which reflected a similar PCB-mediated inhibitory effect on AFB₁ carcinogenesis in trout in vivo. Cyclopropenoid fatty acids (CPFAs) present in the diet (0-600 ppm) were shown to have no effect on in vitro mutagenesis of AFB₁, indicating CPFAs may not significantly alter in vivo initiation of AFB₁ carcinogenesis

Altered Gene Response to Aflatoxin B\u3csub\u3e1\u3c/sub\u3e in the Spleens of Susceptible and Resistant Turkeys

Susceptibility and/or resistance to aflatoxin B1 (AFB1) is a threshold trait governed principally by glutathione S transferase (GST)-mediated detoxification. In poultry, domesticated turkeys are highly sensitive to AFB1, most likely due to dysfunction in hepatic GSTs. In contrast, wild turkeys are comparatively resistant to aflatoxicosis due to the presence of functional hepatic GSTAs and other possible physiological and immunological interactions. The underlying genetic basis for the disparate GST function in turkeys is unknown as are the broader molecular interactions that control the systemic response. This study quantifies the effects of dietary AFB1 on gene expression in the turkey spleen, specifically contrasting genetically distinct domesticated (DT, susceptible) and Eastern wild (EW, resistant) birds. Male turkey poults were subjected to a short-term AFB1 treatment protocol with feed supplemented with 320 ppb AFB1 beginning on day 15 of age and continuing for 14 days. Spleen tissues were harvested and subjected to deep RNA sequencing and transcriptome analysis. Analysis of differential gene expression found the effects of AFB1 treatment on the spleen transcriptomes considerably more prominent in the DT birds compared to EW. However, expression of the differentially expressed genes (DEGs) was directionally biased, with the majority showing higher expression in EW (i.e., down-regulation in DT). Significantly altered pathways included FXR/RXR and LXR/RXR activation, coagulation system, prothrombin activation, acute phase response, and atherosclerosis signaling. Differential extra-hepatic expression of acute phase protein genes was confirmed by quantitative real time PCR (qRT-PCR) in the original experiment and additional turkey lines. Results demonstrate that wild turkeys possess a capacity to more effectively respond to AFB1exposure

Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys

The nearly-ubiquitous food and feed-borne mycotoxin aflatoxin B1 (AFB1) is carcinogenic and mutagenic, posing a food safety threat to humans and animals. One of the most susceptible animal species known and thus a good model for characterizing toxicological pathways, is the domesticated turkey (DT), a condition likely due, at least in part, to deficient hepatic AFB1-detoxifying alpha-class glutathione S-transferases (GSTAs). Conversely, wild turkeys (Eastern wild, EW) are relatively resistant to the hepatotoxic, hepatocarcinogenic and immunosuppressive effects of AFB1 owing to functional gene expression and presence of functional hepatic GSTAs. This study was designed to compare the responses in gene expression in the gastrointestinal tract between DT (susceptible phenotype) and EW (resistant phenotype) following dietary AFB1 challenge (320 ppb for 14 days); specifically in cecal tonsil which functions in both nutrient absorption and gut immunity. RNAseq and gene expression analysis revealed significant differential gene expression in AFB1-treated animals compared to control-fed domestic and wild birds and in within-treatment comparisons between bird types. Significantly upregulated expression of the primary hepatic AFB1-activating P450 (CYP1A5) as well as transcriptional changes in tight junction proteins were observed in AFB1-treated birds. Numerous pro-inflammatory cytokines, TGF-β and EGF were significantly down regulated by AFB1 treatment in DT birds and pathway analysis suggested suppression of enteroendocrine cells. Conversely, AFB1 treatment modified significantly fewer unique genes in EW birds; among these were genes involved in lipid synthesis and metabolism and immune response. This is the first investigation of the effects of AFB1 on the turkey gastro-intestinal tract. Results suggest that in addition to the hepatic transcriptome, animal resistance to this mycotoxin occurs in organ systems outside the liver, specifically as a refractory gastrointestinal tract

Multi-Platform Next-Generation Sequencing of the Domestic Turkey (Meleagris gallopavo): Genome Assembly and Analysis

The combined application of next-generation sequencing platforms has provided an economical approach to unlocking the potential of the turkey genome

Alternaria Toxins

Mycotoxins and Phytoalexins provides a balanced discussion of the health effects of major mycotoxins and phytoalexins, as well as other significant plant toxins. The book features information on toxicologic effects, occurrence, chemistry, and the fate of these toxic chemicals. Mycotoxins and Phytoalexins will be useful to health professionals (including clinicians), mycologists, toxicologists, chemists, pharmacologists, plant pathologists, and food scientists

Non-Hepatic Effects and Biotransformations of Aflatoxin B1

Aflatoxins, natural fungal toxins found in foods and animal feeds, have great public health significance. This book presents the basic and applied toxicology of aflatoxins, including analytical identification, agricultural and veterinary implications, toxicology and carcinogenesis in humans, and economic and regulatory problems associated with aflatoxin contamination and control

Natural Toxins

Now in a thoroughly-updated and expanded second edition, Wiley Encyclopedia of Food Science and Technology covers fundamental concepts and practical requirements in food science, as well as cutting-edge technological and industry information. The encyclopedia features A-to-Z coverage of all aspects of food science, including: the properties, analysis, and processing of foods; genetic engineering of new food products; and nutrition. In addition, nontechnical information is included, such as descriptions of selected scientific institutions, and research and development in government agencies. Like the first edition, this Second Edition will become the standard reference for food scientists, bioengineers, and biotechnologists

Aflatoxins

Mycotoxins and Phytoalexins provides a balanced discussion of the health effects of major mycotoxins and phytoalexins, as well as other significant plant toxins. The book features information on toxicologic effects, occurrence, chemistry, and the fate of these toxic chemicals. Mycotoxins and Phytoalexins will be useful to health professionals (including clinicians), mycologists, toxicologists, chemists, pharmacologists, plant pathologists, and food scientists