1. Mixed exposure to haloacetaldehyde disinfection by-products exacerbates lipid aggregation in the liver of mice.
- Author
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Qiu, Meiyue, Yang, Lili, Jiang, Zhiqiang, Chen, Yu, Liu, Qinxin, Wang, Xia, and Qu, Weidong
- Subjects
DISINFECTION by-product ,FATTY acid synthases ,NON-alcoholic fatty liver disease ,POISONS ,CARNITINE palmitoyltransferase ,PEROXISOME proliferator-activated receptors ,ACETYLCOENZYME A - Abstract
Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HAL, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of DNL pathway, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPAR α). Exposure to 1000X realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mice livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice. [Display omitted] • Haloacetaldehydes disinfection by-products (HALs-DBPs) are hepatotoxic. • HALs-DBPs significantly increased liver and serum triglycerides in C57B/6J mice. • Lipid metabolism and liver function were affected by HALs-DBPs in finished water. • HALs-DBPs induced phenotypes of non-alcohol fat liver disease, lipid accumulation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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