PROTECTIVE EFFECT OF QUERCETIN AGAINST STATINS INDUCED-HEPATOTOXICITY IN CELL LINE

Abstract

Objective: Statins are the most prescribed lipid lowering agents and consequently they prevent obstructive cardiovascular events in the world. Severe adverse effects of statins, involving myopathy and hepatotoxicity, sometimes limit their usage as lipid lowering agents. We now investigate the toxicity of statins and prove the protective effect of quercetin against statins toxicity in cell line. Methods: Human hepatocellular carcinoma cells HepG2 were used in this study were cultured at 37℃ in 5% CO2, in Roswell Park Memorial Institute medium (RPMI 1640) and were supplemented with 10% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 mg/mL streptomycin. HepG2 cells were cultured with some of statins as Atorvastatin, Simvastatin and Rosuvastatin with 10µM concentration with and without pretreatment with 10, 20, 40µM quercetin 4 hours before the addition of statins, then cell line was incubated for 24 and 48 hours. Toxicity of statins was determined by cell viability assay (MTT assay), ALT&AST level assay, lipid peroxidation assay by Malondialdehyde (MDA) and Immunofluorescence staining assay using DAPI. Results: ALT&AST levels were significantly increased after the addition of statins in HepG2 cells when compared with the control group (DMSO 0.1%), and ALT&AST levels were significantly decreased with pretreatment of the cells with quercetin 4 hours before the addition of statins in a dose-dependent manner when compared with statin group. Cell viability percentage (MTT concentration) was decreased significantly after the addition of statins to HepG2 cells when compared with the control group, and MTT concentration was significantly increased with pretreatment of the cells with quercetin 4 hours before the addition of statins in a dose-dependent manner when compared with statin group. MDA concentrations increased significantly after the addition of statins to HepG2 cells when compared with the control group, and decreased when the cells were pretreated with quercetin 4 hours before the addition of statins in a dose-dependent manner when compared with statin group. Statins cause cellular oxidative damage by liberating reactive oxygen species, and the cellular damage was prevented when the cells pretreated with quercetin 4 hours before addition of statins. Conclusions: We found that, quercetin shall protect HepG2 cells from statins-induced hepatotoxicity with 10, 20, 40µM concentrations without significant difference between 20 and 40µM concentrations, and may be developed as a therapeutic agent for possible statins toxicity.