Beneficial effects of combination therapy with testosterone and hydrogen sulfide by reducing oxidative stress and apoptosis: Rat experimental varicocele model

Background: Despite the effectiveness of testosterone therapy in conditions associated with testosterone deficiency, including varicocele, several dose-dependent side effects limit the clinical use of testosterone therapy. Hydrogen sulfide, a toxic gas in high concentrations but a beneficial molecule in low concentrations, acts as both a major effector and an important inducer of testosterone. Objective: This study investigated whether a subeffective dose of testosterone combined with a subeffective dose of hydrogen sulfide donor sodium hydrosulfide (NaHS) can be effective in an experimental varicocele model through a possible additive effect. Materials and Methods: ۳۰ Wistar rats weighing ۲۰۰-۲۵۰ gr were divided into ۵ groups as (n = ۶/each): sham, varicocele, testosterone (۲۰۰ µg/kg, ۵ times per wk for ۴ consecutive wk), NaHS (۱۵ μmol/L, daily for ۴ consecutive wk) and testosterone + NaHS (۲۰۰ µg/kg, ۵ times per wk + ۱۵ μmol/L, daily, both for ۴ consecutive wk). All animals, except in the sham group, underwent varicocele induction. Results: The coadministration of testosterone and NaHS significantly increased serum testosterone (۱۰.۲۳ ± ۰.۹۵, p = ۰.۰۱), testicular H۲S levels (۶۰۸.۹۴ ± ۲۱.۰۹, p < ۰.۰۰۱), and testicular superoxide dismutase activity (۶۶.۱۴ ± ۱.۵۶, p < ۰.۰۰۱), decreased malondialdehyde levels (۰.۷۷ ± ۰.۵۲, p < ۰.۰۰۱), and B-cell lymphoma ۲-associated X protein to B-cell lymphoma ۲ (۰.۱۶ ± ۰.۰۱, p < ۰.۰۰۱) protein expression ratio in the testicular tissues and improved sperm parameters and testicular histopathology compared to the varicocele group. Conclusion: The combination therapy of subeffective doses of testosterone and NaHS can attenuate the varicocele-induced damages by reducing testicular oxidative stress and apoptosis and thus can be considered an effective approach with fewer side effects.

کلیدواژه ها:

Apoptosis genes ، Hydrogen sulfide ، Oxidative stress ، Sperm count ، Testosterone ، Varicocele. ، ژن­های آپوپتوتیک ، سولفید هیدروژن ، استرس اکسیداتیو ، تعداد اسپرم ، تستوسترون ، واریکوسل.