Roles of stress response‐related signaling and its contribution to the toxicity of zearalenone in mammals

Abstract

Zearalenone (ZEA) is a mycotoxin frequently found in cereal crops and cerealderived foodstuffs worldwide. It affects plant productivity, and is also a serious hazard to humans and animals if being exposed to food/feed contaminated by ZEA. Studies over the last decade have shown that the toxicity of ZEA in animals is mainly mediated by the various stress responses, such as endoplasmic reticulum (ER) stress, oxidative stress, and others. Accumulating evidence shows that oxidative stress and ER stress signaling are actively implicated in and contributes to the pathophysiology of various diseases. Biochemically, the deleterious effects of ZEA are associated with apoptosis, DNA damage, and lipid peroxidation by regulating the expression of genes implicated in these biological processes. Despite these findings, the underlying mechanisms responsible for these alterations remain unclear. This review summarized the characteristics, metabolism, toxicity and the deleterious effects of ZEA exposure in various tissues of animals. Stress response signaling implicated in the toxicity as well as potential therapeutic options with the ability to reduce the deleterious effects of ZEA in animals were highlighted and discussed.

Zearalenone Decreases Food Intake by Disrupting the Gut–Liver–Hypothalamus Axis Signaling via Bile Acids

“…ZEN is a mycotoxin commonly occurring in crops that can harm humans and farm animals . Most studies mainly attributed its toxicity to its induction of endoplasmic reticulum stress and oxidative stress .…”

“…ZEN is a mycotoxin commonly occurring in crops that can harm humans and farm animals. 1 Most studies mainly attributed its toxicity to its induction of endoplasmic reticulum stress and oxidative stress. 1 In this study, ZEN decreased the expression levels of hepatic FXR, a key protein that participates in the regulation of BA homeostasis, 4,36 and it also reduced the expression levels of ERα.…”

“…To confirm the results of the experiments described above, we treated female rats with a low dose of ZEN (40 mg/kg feed). ZEN poses the greatest harm to reproductivity of female animals, so female rats were chosen as models in subsequent experiments . The actual measured concentration of ZEN was 35.7 mg/kg of feed.…”

“…Zearalenone (ZEN) is a common mycotoxin produced by Fusarium species and exhibits a potent estrogenic activity. It contaminates a variety of important grains, such as maize, barley, wheat, and others, and thus threatens the health of humans and farm animals . Most studies attribute its toxicity to its induction of endoplasmic reticulum stress and oxidative stress, but ZEN differs from other mycotoxins in that it has high estrogenic potency .…”

“…It contaminates a variety of important grains, such as maize, barley, wheat, and others, and thus threatens the health of humans and farm animals . Most studies attribute its toxicity to its induction of endoplasmic reticulum stress and oxidative stress, but ZEN differs from other mycotoxins in that it has high estrogenic potency . In particular, α-zearalenol (α-ZOL), a metabolite of ZEN, can exhibit about 70% of the estrogen potency of 17-β-estradiol .…”