Co-administration of atorvastatin with piperine induces reproductive toxicity in male Wistar rats through oxidative stress induction and downregulation of StAR, CYP11a1, 3(3HSD and 17(3HSD genes

Atorvastatin is a statin group of medicine that inhibits biosynthesis of cholesterol and mainly prescribed for treating cardiovascular diseases. Black pepper is a one of the mostly used spices that contains an alkaloid called piperine in its fruits which is known to cause male reproductive toxicity. Both atorvastatin and black pepper (piperine) are randomly consumed by the patients of chronic hyperlipidemia and it is important to know the synergistic effects of atorvastatin and piperine on male fertility parameters. Twenty rats were taken for the study and divided into four groups each containing five rats. Group I served as a control, group II animals are treated with atorvastatin (ATR) (8 mg/kg BW), group III animals received piperine (PIP) (10 mg/kg BW) and group IV animals were co-administered with piperine (10 mg/kg BW) and atorvastatin (8 mg/kg BW). All treatments were done by using water suspension of atorvastatin and piperine and using oral gavage for consecutive 28 days and thereafter assessed for gravimetric and histomorphometry analysis, sperm motility and morphology, ROS generation, anti-oxidant enzymes, serum testosterone quantification, qRTPCR (StAR, CYP11a1, 3(3HSD and 17(3HSD genes) and toluidine blue staining for analyzing chromatin integrity of spermatozoa. The results showed that coadministration of ATR+PIP significantly reduced body weight, changed in GSI also found. Activities of major two antioxidant enzymes (SOD and Catalase) were found to reduce whereas levels of TBARS and ROS in testicular tissues increased significantly. The study found that combined administration of atorvastatin and piperine negatively impacted male fertility potential, causing reproductive toxicity.