Mechanism of subchronic vinyl chloride exposure combined with a high‐fat diet on hepatic steatosis

Abstract

Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid‐induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800 mg/m3) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 μM) on hepatic steatosis of high‐fat diet (HFD)‐fed mice and palmitic acid (PA, 100 μM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single‐exposure groups (HFD group, low‐dose VC group, and high‐dose VC group). Moreover, VC enhanced HFD‐induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element‐binding protein 1 (SREBP‐1) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD‐fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis‐related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.

Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver

“…Alcohol abuse is a prototypical situation associated with CYP2E1 induction and CYP2E1-generated ROS but there is increasing evidence that other xenobiotics can also enhance CYP2E1 expression and activity in liver or other tissues. For instance, this has been shown for the industrial toxicants vinyl chloride and 1,4-dioxane [ 80 , 81 ] and for different pesticides including methoxychlor, phoxim, atrazine, maneb and paraquat [ 82 , 83 , 84 , 85 , 86 ]. A recent study also reported hepatic CYP2E1 induction in rats treated with the endocrine disruptor bisphenol A [ 87 ].…”

Plastic compounds and liver diseases: Whether bisphenol A is the only culprit

“…124 The liver steatosis was further augmented in HFD mice and PA-induced hepatic cell line exposed to PVC MPs. 125 In a recent review, data linking PVC to liver toxicity are highest among all microplastics. 126 LDPE microplastics used in commercially available ready-to-eat storage containers were found to migrate into the food product.…”

“…Another study in a mouse model revealed the altered gut microbiota and liver injury when exposed to PVC MPs 124 . The liver steatosis was further augmented in HFD mice and PA‐induced hepatic cell line exposed to PVC MPs 125 . In a recent review, data linking PVC to liver toxicity are highest among all microplastics 126…”