Simvastatin affects Nrf2/MAPK signaling pathway and hepatic histological structure change in Gambusia affinis

Simvastatin (SV) is a typical lipid-lowering agent detected widely in waters, so its latent toxic effects to fish are deserved of concern. The purposes of this study aim at revealing the responses of antioxidant system in mosquitofish (Gambusia affinis) under SV exposure. Transcriptional expressions of oxidative stress-related key transcriptional factor Nrf2 and its downstream genes in mosquitofish were determined under SV exposure for different time. Partly related enzymatic activities, Nrf2 and MAPK protein expressions were also addressed in the same conditions, and histological changes in liver tissues were investigated too. Results showed that Nrf2 mRNA increased with the rising SV concentrations at 3 d and 7 d, displaying typical dose-dependent relationship, and Nrf2 protein by WB showed consistency with transcriptional changes to some degree. Comparatively, responses of gene expressions were more sensitive than enzymatic changes. The histological changes in the mosquitofish liver exposed to SV for 7 d indicated the potential adverse effects of statins. This work demonstrated that SV in aquatic environment could affect the transcriptional expression of antioxidant system, partly related enzymatic activity, and hepatic structure in the mosquitofish, revealing its potential risk on non-target organisms and environmental safety.