Objectives: Reduced male fertility is highly prevalent with hypercholesterolaemia. Though statins are drugs of choice for hypercholesterolaemia, their effect on male fertility is still controversial and dose-dependent. Grape seed extract (GSE) possess hypocholesterolemic and testicular protective effects. Thus, this study aimed to investigate the effects of low-dose atorvastatin (ATV) on male infertility in hypercholesterolaemic rats and assess the additional value of combining ATV with GSE.
Methods: Male rats were randomized into four groups. The normal group was fed a standard diet. The remaining groups were fed a high-fat diet (HFD) for 1 month to induce hypercholesterolaemia. Two HFD groups were administered either ATV (1 mg/kg) alone or combined with GSE (200 mg/kg) orally for 65 days, while the third group served as HFD control.
Key findings: Treatment with ATV or ATV/GSE attenuated dyslipidemia-induced alteration in serum HDL-cholesterol, LDL-cholesterol, and total cholesterol. ATV enhanced serum testosterone, sperm count and motility and fertility index. The effect on testosterone and sperm count was more pronounced by ATV/GSE. Moreover, ATV reduced testicular malondialdehyde, nitric oxide, caspase-9 and caspase-3 while elevated reduced glutathione and superoxide dismutase along with catalase activity. Noteworthy, GSE/ATV induced more powerful antioxidant and anti-apoptotic effects.
Conclusion: GSE enhanced ATV's protective effect against hypercholesterolaemia-induced infertility via antioxidant and anti-apoptotic mechanisms.
Keywords: antioxidant; atorvastatin; caspases; grape seed extract; hypercholesterolaemia; male fertility.
© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.