Fenofibrate ameliorated atorvastatin and piperine-induced ROS mediated reproductive toxicity in male Wistar rats

Abstract

Atorvastatin and fenofibrate are well-known lipid-lowering drugs. Atorvastatin acts by reducing the production of cholesterol through the inhibition of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A reductase) enzyme, whereas fenofibrate is a PPAR-α agonist. Piperine is an alkaloid mostly found in black pepper fruits. The present study was planned to evaluate the activities of atorvastatin, fenofibrate, and piperine on the male reproductive system. A total of 35 male Wistar rats were obtained for the experiment. Rats were randomly divided into 7 groups, each group with 5 rats. The experiment was run for 28 days. Group I rat got normal meals for 28 days; Group II received atorvastatin (08 mg/kg/day); Group III received piperine (10 mg/kg/day); and Group IV received fenofibrate (20 mg/kg/day). Group V received atorvastatin (8 mg/kg/day) and piperine (10 mg/kg/day); Group VI received piperine (10 mg/kg/day) and fenofibrate (20 mg/kg/day). VII received fenofibrate (20 mg/kg bw/day) and atorvastatin (8 mg/kg/day). After sacrifice, serum and testicular cholesterol and testosterone levels assessed by ELISA, ROS generation analysed by using flow cytometry, MDA, SOD, and catalase were measured. Histological, sperm-parameter analysis, and spermatogenic evaluations were also done. Activities of atorvastatin and piperine revealed reproductive toxicity upon treatment. Fenofibrate treatment, along with atorvastatin and piperine, showed protective effects. In conclusion, atorvastatin and piperine affected reproductive potential, whereas fenofibrate might have protective efficacy against atorvastatin and piperine-induced reproductive toxicity.