2,3,7,8-Tetrachlorodibenzo-p-dioxin induces liver lipid metabolism disorder via the ROS/AMPK/CD36 signaling pathway.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is widely considered as the most toxic and common carcinogen in the world. Exposure to TCDD causes liver lipid metabolism disorder and steatosis. However, the molecular mechanism of TCDD-induced liver lipid accumulation is not completely clear. Here, we found that a 5 µg/kg TCDD exposure for 3 weeks induced hepatocyte lipid deposition, increased CD36 expression, and promoted AMP-activated protein kinase (AMPK) ɑ phosphorylation in the liver of C57BL/6J mice. Furthermore, sulfo-N-succinimidyl oleate, a CD36 inhibiter, blunted TCDD-induced lipid deposition in Huh7 cells, confirming the critical role of CD36 in TCDD-induced hepatic steatosis. In terms of molecular mechanisms, we found that TCDD exposure increased reactive oxygen species (ROS) levels in Huh7 cells, which activated AMPK. Moreover, the activated AMPK upregulated CD36 expression. Therefore, we can see that the increase in CD36 expression induced by TCDD was regulated by ROS/AMPK/CD36 signaling pathway. Our results help to clarify the molecular mechanism of TCDD-induced hepatic steatosis.

Antimony trichloride induces a loss of cell viability via reactive oxygen species-dependent autophagy in A549 cells.

Antimony (Sb) is one of the most prevalent heavy metals and frequently leads to biological toxicity. Although autophagy is believed to be involved in metal-associated cytotoxicity, there is no evidence of its involvement following exposure. Moreover, the underlying mechanism of autophagy remains unclear. In this study, treatment with antimony trichloride caused autophagy in a dose- and time-dependent manner in A549 cells but did not affect the level of Atg5 or Atg7 mRNA expression. Furthermore, Sb enhanced autophagic flux while upregulating p62 gene and protein levels. The classic mechanistic target of rapamycin (mTOR) pathway is not involved in Sb-induced autophagy. However, Sb-induced autophagy and the upregulation of p62 were inhibited by treatment with the antioxidant N-acetylcysteine (NAC). Subsequent analyses demonstrated that the inhibition of autophagy protected A549 cells from a loss of cell viability, while the activation of autophagy by rapamycin had the opposite effect. These data suggest that reactive oxygen species-dependent autophagy mediates Sb-stimulated cell viability loss in A549 cells.