AFB-induced mice liver injury involves mitochondrial dysfunction mediated by mitochondrial biogenesis inhibition.

Aflatoxin B1 (AFB) pollutes foodstuffs and feeds, causing a food safety problem and seriously endangering human and animal health. Liver is the principal organ for AFB accumulation and biotransformation, during which AFB can cause acute and chronic liver damage, however, the specific mechanism is not completely clear. Mitochondria are the primary organelle of cellular bio-oxidation, providing 95% energy for liver to execute its multiple functions. Therefore, we speculated that mitochondrial dysfunction is involved in AFB-induced liver injury. To verify the hypothesis, a total of eighty healthy male mice were randomly divided into four groups on average, and exposed with 0, 0.375, 0.75 and 1.5 mg/kg body weight AFB by intragastric administration for 30 d. The results displayed that AFB triggered liver injury accompanied by oxidative stress. AFB exposure also damaged mitochondria structure, decreased mitochondrial membrane potential (MMP), as well as increased cytoplasmic cytochrome c (Cyt-c) protein expression, Bax, p53, Caspase-3/9 protein and/or mRNA expression levels and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling (TUNEL) staining positive cells in mice liver. Meanwhile, AFB exposure elevated pyruvate content, inhibited tricarboxylic acid (TCA) cycle rate-limiting enzymes and electron transport chain (ETC) complexes I-V activities, disturbed ETC complexes I-V subunits mRNA expression levels and reduced adenosine triphosphate (ATP) level in mice liver. These results indicated that AFB destroyed mitochondrial structure, activated mitochondrion-dependent apoptosis and induced mitochondrial dysfunction. In addition, AFB disrupted mitochondrial biogenesis, presented as the abnormalities of protein and/or gene expression levels of voltage dependent anion channel protein 1 (VDAC1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (Nrf1) and mitochondrial transcription factor A (Tfam). This may contribute to hepatic and mitochondrial lesions induced by AFB. These results provide a new perspective for elucidating the mechanisms of AFB hepatotoxicity.