zearalenone and Liver-Diseases

Topics: Abnormalities, Drug-Induced; Aflatoxins; Animals; Climate; Female; Food Analysis; Food Contamination; Gastrointestinal Diseases; Genital Diseases, Female; Humans; Liver Diseases; Mycotoxins; Neoplasms; Neuromuscular Diseases; Plant Poisoning; Respiratory Tract Diseases; Skin Diseases; Sporidesmins; Trichothecenes; Zearalenone

Outbreaks of liver disease in horses are common but the etiology of most remains unknown. Forage mycotoxins have been suspected to be a cause.. To examine the association between outbreaks of liver disease and the presence of mycotoxins in forage stored on the same premises.. Premises were identified where ≥4 horses were contemporaneously affected by liver disease, and a control group was formed from premises where ≥4 horses had been examined and found to have no evidence of liver disease.. Forage was collected from 29 case and 12 control premises. The forage was analyzed for mycotoxin content using a liquid chromatography/mass spectrometry method, targeting 54 mycotoxins. The presence and distribution of mycotoxins between case and control samples was compared.. Mycotoxins were found in 23/29 (79%) case samples and 10/12 (83%) control samples (P > .99; relative risk, 0.93; 95% confidence interval [CI], 0.64-1.75). Median (interquartile range [IQR]) total mycotoxin concentration was similar in case and control samples (85.8 μg/kg [1.6-268] vs. 315 μg/kg [6.3-860]; P = .16). Ten mycotoxins were found exclusively in case premises comprising fumonisin B1, 15-acetyldeoxynivalenol, deoxynivalenol, zearalenone, aflatoxins B1 and G1, methylergonovine, nivalenol, verruculogen, and wortmannin. The median (IQR) concentration of fumonisin B1 was significantly higher in case versus control samples (0 μg/kg [0-81.7] vs. 0 μg/kg [0-0]; P = .04).. Several mycotoxins with known hepatotoxic potential were found, alone or in combination, exclusively at case premises, consistent with the hypothesis that forage-associated mycotoxicosis may be a cause of outbreaks of liver disease in horses in the United Kingdom.

Topics: Animals; Food Contamination; Horse Diseases; Horses; Liver Diseases; Mycotoxins; United Kingdom; Zearalenone

It was hypothesized that a mycotoxin binder, Grainsure E, would inhibit adverse effects of a mixture of fumonisin B1, deoxynivalenol, and zearalenone in rats. For 14 and 28 days, 8-10 Sprague-Dawley rats were fed control diet, Grainsure E (0.5%), toxins (7 μg fumonisin B1/g, 8 μg of deoxynivalenol/g and 0.2 μg of zearalenone/g), toxins (12 μg of fumonisin B1/g, 9 μg of deoxynivalenol/g, and 0.2 μg of zearalenone/g + Grainsure E), or pair-fed to control for food intake of toxin-fed rats. After 28 days, decreased body weight gain was prevented by Grainsure E in toxin-fed female rats, indicating partial protection against deoxynivalenol and fumonisin B1. Two effects of fumonisin B1 were partly prevented by Grainsure E in toxin-fed rats, increased plasma alanine transaminase (ALT) and urinary sphinganine/sphingosine, but sphinganine/sphingosine increase was not prevented in females at the latter time point. Grainsure E prevented some effects of fumonisin B1 and deoxynivalenol in rats.

Topics: Animals; Chemical and Drug Induced Liver Injury; Diet; Female; Fumonisins; Kidney Diseases; Liver Diseases; Male; Mycotoxins; Rats; Rats, Sprague-Dawley; Trichothecenes; Zearalenone

Zearalenone (ZEN) is a fusarial mycotoxin with several adverse effects in laboratory and domestic animals including mainly estrogenicity. While most ZEN toxic effects have been quite well investigated, little is known regarding its mechanism of toxicity. Our previous investigations have shown the involvement of cytotoxicity, inhibition of macromolecules synthesis as well as genotoxicity. However, there are no available data regarding the involvement of the oxidative stress pathway in ZEN toxicity. In this context, the aim of this study was to find out whether ZEN induces oxidative cell damage. Using human hepatocytes Hep G2 cells, ZEN-induced stress response is monitored at several levels in these cells. ZEN mediated induction of oxidative DNA damage (comet assay using the repair enzymes), modulation of gluthatione (GSH), cytotoxicity (growth inhibition) and the oxidative stress responsive gene Hsp 70 and Hsp 90 were investigated with respect to concentration and time dependency. Hep G2 cells respond to ZEN exposure by loss of cell viability, induction of oxidative DNA damage, GSH depletion and Hsp 70 and Hsp 90 induction already at concentrations, which are not yet cytotoxic. The perturbation of the oxidative status was further confirmed by the significant reduction of the induced oxidative DNA damage as well as stress protein induction when cells were pre-treated with Vitamin E prior to exposure to ZEN. Our study clearly demonstrates that oxidative damage is likely to be evoked as one of the main pathway of ZEN toxicity. This oxidative damage may therefore be an initiating event and contribute, at least in part, to the mechanism of ZEN different genotoxic and cytotoxic effects.

Topics: Antioxidants; Cell Line, Tumor; Cell Survival; Chemical and Drug Induced Liver Injury; Comet Assay; DNA Damage; Glutathione; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Humans; Immunoblotting; Liver; Liver Diseases; Mycotoxins; Oxidative Stress; Statistics, Nonparametric; Vitamin E; Zearalenone

Feeding experiments with diets containing Fusarium toxin-contaminated wheat were conducted to clarify the pathogenesis of enzymatic and histopathological effects of Fusarium toxins on porcine liver cells. A total of 36 prepuberal gilts were divided into four groups and fed diets with increasing proportions of Fusarium toxin-contaminated wheat at a total wheat proportion of 40% over a period of 35 days. The concentrations of the indicator toxins deoxynivalenol (DON) and zearalenone (ZON) which were analyzed by HPLC methods were 210/4, 3070/88, 6100/235, and 9570/358 microg/kg in the diets fed to groups I-IV, respectively. The feeding of mycotoxin-contaminated diets did not cause gross pathological findings in the livers of the animals. Liver tissues were subjected to enzymatic, histological, and ultrastructural examinations. The percentages of the stained areas in periodic acid-Schiff (PAS), Berlin-Blue, and Masson Goldner's trichrome stainings were calculated using the AnalySIS 3.4-system. Significant histopathological findings of alterations with varying degrees in glycogen reduction and increase of hemosiderin particles were found in the liver cells of groups II, III and IV. The thickness of interlobular connective tissue septum in liver cells was significantly increased in groups III and IV. Qualitative ultrastructural alterations were observed in hepatocytes of gilts in groups III and IV. Dependent upon the mycotoxin concentration in the diet, the hepatocytes developed a dose-dependent, extensive, smooth endoplasmic reticulum, exhibited loss of ribosomes, and acquired an increased number of fatty and autophagic vacuoles. However, liver damage as measured by prominent elevated transaminase activities in serum was not detected. Together, the histopathological results provide evidence of liver dysfunction in the absence of clinical signs, especially in pigs fed higher concentrations of Fusarium toxin-contaminated wheat.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Ca(2+) Mg(2+)-ATPase; Collagen; Edible Grain; Female; Fusarium; gamma-Glutamyltransferase; Hemosiderin; Hepatocytes; Liver Diseases; Liver Glycogen; Microscopy, Electron; Swine; Swine Diseases; Trichothecenes; Triticum; Zearalenone