Rosuvastatin calcium and pravastatin sodium regulate the antioxidant system in zebrafish liver through the PI3K/Nrf2/ARE signaling pathway
- Comp Biochem Physiol C Toxicol Pharmacol. 2026 Jun 4:110596. doi: 10.1016/j.cbpc.2026.110596.
- 1. College of Life Sciences, North China University of Technology, Tangshan, 063210, PR China.
- 2. College of Life Sciences, North China University of Technology, Tangshan, 063210, PR China. Electronic address: [email protected].
Rosuvastatin calcium (ROV) and pravastatin sodium (PRA) are common drugs used for the treatment and prevention of cardiovascular diseases. They have been frequently detected in the global aquatic environment, but their toxic effects and molecular mechanisms on the antioxidant system of fish remain unclear. In this study, zebrafish were exposed to ROV or PRA for 48 h to investigate their effects on the hepatic antioxidant response system of zebrafish and the possible underlying molecular mechanisms. The results showed that after exposure to the two drugs, the levels of Reactive Oxygen Species (ROS), glutathione (GSH), and malondialdehyde (MDA) increased, while the activities of catalase (CAT) and superoxide dismutase (SOD) were inhibited. Exposure to ROV (5 mg/L) upregulated the activities of Glutathione Peroxidase (GPx) and Glutathione S-transferase (GST), as well as the mRNA levels of phosphatidylinositol 3-kinase (PI3K) and CAT. However, the protein levels of nuclear factor erythroid 2-like protein (Nrf2) and SOD were suppressed. Exposure to PRA (10 mg/L) also increased the mRNA levels of PI3K, CAT, and GPx, while inhibiting Nrf2 and SOD proteins. The inhibitory effects on Nrf2 and SOD proteins were reversed after the addition of the PI3K Activator 740YP. Molecular docking showed that both ROV and PRA could bind stably to PI3K. In conclusion, both ROV and PRA can induce hepatic oxidative damage in zebrafish, and the mechanism may be related to the disruption of the PI3K-mediated Nrf2/ARE pathway.