Sodium arsenite accelerates D-galactose-induced aging in the testis of the rat: Evidence for mitochondrial oxidative damage, NF-kB, JNK, and apoptosis pathways.

Aging inhibits male reproductive function and can have an impact on fertility. This study elucidated the accelerating role of sodium arsenite (As) on D-galactose-induced reproductive aging in male rats. The rats in the study are divided into nine groups. Group I is young control. Group II is naturally aged 24-month-old rats, other animal groups received As (0.5, 1, and 2 mg/kg/day, i.p.) and/or D-galactose (DG) (50 mg/kg/day, i.p.) for 8 weeks. Then, sperm parameters, histopathological manifestations, oxidative stress markers, and gene expression of inflammatory factors (TNF-α, IL-6, and NF-ƙB), apoptosis-related genes (Bcl-2 and Bax), and C-Jun N-terminal kinase (JNK) were evaluated in testis tissue. As (1 and 2 mg/kg) induced significant changes in evaluated factors compared to control group. Co-treatment with DG and As caused morphological changes as well as a significant decrease in sperm motility and count. In DG + As group, histopathological changes were also more obvious. Moreover, as compared to the DG group, co-treated animals exhibited a significant increase in oxidant markers and a decrease in antioxidant levels. Accordingly, DG co-exposure with As markedly enhances the expressions of TNF-α, IL-6, and NF-ƙB compared to DG alone. Likewise, in the testis of rats treated with As3 + plus DG compared to DG alone, there was up-regulation of Bax (pro-apoptotic), down-regulation of Bcl-2 (anti-apoptotic), and elevation of JNK expression. These findings suggest sodium arsenite as an accelerating cause for D-galactose-induced aging process in testis tissue.