Aflatoxin B1-induced hepatotoxicity through mitochondrial dysfunction, oxidative stress, and inflammation as central pathological mechanisms: A review of experimental evidence.

Abstract

Aflatoxin B₁ (AFB₁) is a class of mycotoxin known to contaminate agricultural products, animal feed and animal food products, subsequently causing detrimental effects on human and animal health. AFB₁ is the most common and potent aflatoxin found in food and contributes significantly to liver injury as well as the development of hepatocellular carcinoma. Although the liver is a primary target organ for AFB₁ toxicity and biotransformation, underlying mechanisms implicated in liver injuries induced by these mycotoxins remain to be fully elucidated for therapeutic purposes. This review aims to dissect the complexities of the pathophysiological and molecular mechanisms implicated in hepatotoxicity induced by AFB₁, including mitochondrial dysfunction, oxidative stress and hepatic inflammation. Mechanistically, AFB₁ disrupt mitochondrial bioenergetics and membrane potential, promotes mitochondrial cholesterol trafficking and induces mitophagy. Moreover, mitochondrial dysfunction may lead to hepatic oxidative stress as a consequence of uncontrolled production of reactive oxygen species and defects in the antioxidant defense system. Retrieved experimental evidence also showed that AFB₁ may lead to hepatic inflammation through gut microbiota dysbiosis, the release of DAMPs and cytokines, and immune cell recruitment. Overall, these mechanisms could be utilized as potential targets to extrapolate treatment for liver injury caused by AFB₁.