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Simvastatin affects the PPAR alpha signaling pathway and causes oxidative stress and embryonic development interference in Mugilogobius abei

文献类型： 外文期刊

作者： Wang, Chao 1 ; Tang, Tianli 1 ; Wang, Yimeng 1 ; Nie, Xiangping 1 ; Li, Kaibin 4 ;

作者机构： 1.Jinan Univ, Hydrobiol Res Inst, Dept Ecol, Guangzhou 510632, Peoples R China

2.Jinan Univ, Red Tide Prevent Guangdong Higher Educ Inst, Guangzhou 510632, Peoples R China

3.Jinan Univ, Key Lab Eutrophicat, Guangzhou 510632, Peoples R China

4.Chinese Acad Fishery Sci, Pearl River Fisheries Res Inst, Guangzhou 510380, Peoples R China

关键词： Simvastatin; PPAR alpha; Oxidative stress; Lipid metabolism; Embryonic developmental toxicity

期刊名称：AQUATIC TOXICOLOGY （ 影响因子：4.964； 五年影响因子：5.071 ）

ISSN： 0166-445X

年卷期： 2021 年 239 卷

页码：

收录情况： SCI

摘要： Simvastatin (SV) is a common hypolipidemic drug in clinical medicine that can reduce endogenous cholesterol biosynthesis by inhibiting hydroxyl-methyl-glutaryl coenzyme A reductase. SV took a large market share in the lipid-lowering drugs and it is frequently detected in various water bodies due to its increasing consumption in past years. In the present investigation, we selected a native fish species in the Pearl River Basin in China, Mugilogobius abei (M. abei), to study the effects of SV on non-target aquatic organisms. Results showed that a significant decrease in the volume of adipocytes under SV exposure were observed on oil red O section, and the expression of HMG-CoAR decreased significantly. The mRNA and protein expression of PPAR alpha were significantly up-regulated, the expressions of other genes related to lipid metabolism were up-regulated to varying degrees as well. There was a positive correlation between the concentrations of SV and the protein expressions of plasma phospholipid transfer protein (PLTP) and cholesterolester transfer protein (CETP). In addition, the frozen sections showed that SV led to ROS accumulation in liver in a time and concentration dependent manner. The mRNA and protein expressions of Nrf2 were significantly up-regulated after 24 hours of SV exposure. Some biomarkers associated with antioxidant such as Trx2, TrxR and MDA content were positively correlated with the exposure concentration and time, while the content of GSH decreased sharply. It is noteworthy that the environmentally relevant concentration (0.5 mu g/L) of SV exposure caused delayed embryonic development and deformations, decreased hatching rates. We conclude that SV promotes fat metabolism, gives rise to oxidative stress and has significant toxicity on embryo development in M. abei.

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