Grape seed extract improved the fertility-enhancing effect of atorvastatin in high-fat diet-induced testicular injury in rats: involvement of antioxidant and anti-apoptotic effects

Abstract

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.

In Silico Interactions of Natural and Synthetic Compounds with Key Proteins Involved in Alzheimer’s Disease: Prospects for Designing New Therapeutics Compound

“…Our data suggested hazardous effects of atorvastatin on the reproduction system which is in line with studies conducted on rat and human which reported erectile and testicular dysfunction, altered steroid hormone production, and reducing sperms’ count number (Akdeniz et al 2020 ; Omolaoye et al 2022 ). Also, it is worth mentioning that the mechanism of causing dysfunction in the reproduction system is remained a controversial issue since some studies stated that statins can improve the reproduction system and sperm quality (Abdulwahab et al 2021 ; Davis et al 2015 ; Sadeghi et al 2021 ). Besides, there are several side effects reported in patients who take statins which we have not predicted.…”

Moringa oleifera ethanolic extract ameliorates the testicular dysfunction resulted from HFD‐induced obesity rat model

“…Meanwhile, the reproductive efficiency of the HFD group (G3) was generally compromised, as evidenced by the significant reduction in serum testosterone, and quantitative sperm disorders (reduced sperm cell concentration) and qualitative sperm disorders (reduced sperm viability and motility, and an increased proportion of morphological abnormalities) in rats fed a HFD (Abdulwahab et al., 2020). In a previous study, the aqueous leaf extract of Moringa oleifera enhanced the percentage of non‐capacitated spermatozoa, basic sperm functions, decreased the excess sperm free superoxide production, and maintained the acrosome reaction as well as the integrity of DNA in human (Moichela et al., 2021).…”

Effects of clinical medications on male fertility and prospects for stem cell therapy

“…In studies on rats fed a high-fat diet, statins have a protective effect on male reproductive function. They improve semen quality, increase serum testosterone levels, improve testicular weight loss caused by hyperlipidemia, and increase fertility index ( Abdulwahab et al, 2021 ; Esmail et al, 2020 ; Shalaby et al, 2004 ). These reproductive protective effects may be achieved by enhancing the mTOR signaling pathway and reducing oxidative stress ( Cui et al, 2017 ; Farsani et al, 2018 ; Gurel et al, 2019 ).…”