Arsenic or/and antimony induced mitophagy and apoptosis associated with metabolic abnormalities and oxidative stress in the liver of mice

Arsenic and antimony are coexisting cumulative environmental pollutants that cause severe and extensive biolog-ical toxicity. However, their interactions and toxic mechanisms in the liver remain to be fully elucidated. In this study, a total of sixty 4-week-old mice were divided into four groups and treated with 4 mg/kg arsenic trioxide (ATO) or/and 15 mg/kg antimony (Sb) for 60 days. The results demonstrated that biochemical indicators of hepato-toxicity (ALT, AST, ALP) were upregulated in all treated groups. Additionally, the oxidative burden of the liver was increased in the cotreated groups compared with the individual toxicant-treated groups. Meanwhile, mitochondrial injury, autophagosomes, hepatic-congestion and karyopyknosis were obviously observed in cotreated groups. Addi-tionally, coupled with serum biochemical index (TG, TC), histopathology examination and metabolomics results, we found that cotreatment with ATO and Sb resulted in lipid metabolism disorder and steatosis of liver tissues. Our fur-ther investigation found that the levels of pro-apoptotic (Caspase-3, Caspase-9, Bax, P53, Cytc) and mitophagy (LC3-B, P62, PINK1, Parkin) indexes in the cotreated groups were markedly increased, whereas the levels of anti-apoptosis index (Bcl-2) were decreased. Collectively, these results show that co-exposure to ATO and Sb can cause abnormal liver energy metabolism and oxidative stress. Moreover, mitophagy and apoptosis play important roles in the mech-anisms of arsenic/antimony cytotoxicity to mouse livers. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study demonstrated that co-exposure to arsenic and antimony can result in oxidative damage and mitochondrial injury in the liver, leading to abnormal liver energy metabolism and lipid metabolism disorder. Mitophagy and apoptosis play important roles in the mechanisms of arsenic/antimony cytotoxicity to mouse livers.