Abstract
Atorvastatin (ATV) is a hypolipidemic drug widely detected in the aquatic environment. Nevertheless, limited information is provided about the toxic effects of ATV on estuary or coastal species and the underlying mechanisms. In the present study, the responses of genes expression in pregnane X receptor (PXR) signaling pathway and enzymatic activities in the liver of the estuarine benthic fish (Mugilogobius chulae) were investigated under acute and sub-chronic ATV exposure. Results showed that PXR was significantly inhibited in the highest exposure concentration of ATV for a shorter time (24 h, 500 μg L−1) but induced in a lower concentration (72 h, 5 μg L−1). The downstream genes in PXR signaling pathway such as CYP3A, SULT, UGT, and GST showed similar trends to PXR. P-gp and MRP1 were repressed in most treatments. GCLC associated with GSH synthesis was mostly induced under ATV exposure for a long time (168 h), suggesting that reactive oxygen species (ROS) were generated under ATV exposure. Similarly, GST and SOD enzymatic activities significantly increased in most exposure treatments. Under ATV exposure, SIRT1 and SIRT2 displayed induction to some extent in most treatments, suggesting that SIRTs may affect PXR expression by regulating the acetylation levels of PXR. The investigation demonstrated that ATV exposure affected the expression of the Sirtuin/PXR signaling pathway, thus further interfered adaption of M. chulae to the environment.
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Acknowledgements
The authors would like to thank Central Laboratory, Basic Medical School, Jinan University, China for all the provided help. The authors also would like to thank Guangdong Laboratory Animals Monitoring Institute, China for providing experimental materials. We also want to thank Dr. Peijia Ku (Postdoctoral Research Associate at Oak Ridge National Laboratory, USA) for her help in English language.
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This work was supported by National Natural Science Foundation of China (NSFC 41576110; 31770554).
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Zhao Yufei: methodology, investigation, software, data curation, writing—original draft preparation; Xie Meinan: methodology, investigation, software, data curation, formal analysis; Wang Chao: investigation, software, data curation; Wang Yimeng: investigation, software, data curation; Peng Ying: investigation, data curation, writing—reviewing and editing; Nie Xiangping: conceptualization, writing—reviewing and editing, supervision, funding acquisition, project administration.
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Highlights
• ATV altered the expression of the Sirtuin/PXR signaling pathway in Mugilogobius chulae
• ATV affected the activities of several detoxification and antioxidant-related enzymes in Mugilogobius chulae
• ATV in the aquatic environment may pose unexpected adverse effects to non-target organisms like Mugilogobius chulae
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Zhao, Y., Xie, M., Wang, C. et al. Effects of atorvastatin on the Sirtuin/PXR signaling pathway in Mugilogobius chulae. Environ Sci Pollut Res 30, 60009–60022 (2023). https://doi.org/10.1007/s11356-023-26736-5
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DOI: https://doi.org/10.1007/s11356-023-26736-5