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

Toxicology. 2024 Dec:509:153983. doi: 10.1016/j.tox.2024.153983. Epub 2024 Nov 2.

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.

Keywords: Aflatoxin B(1); Hepatotoxicity; Inflammation; Mitochondrial dysfunction; Oxidative stress.

Publication types

  • Review

MeSH terms

  • Aflatoxin B1* / toxicity
  • Animals
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Chemical and Drug Induced Liver Injury* / pathology
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Oxidative Stress* / drug effects

Substances

  • Aflatoxin B1