In vivo and in silico evaluation of the ameliorative effect of hesperidin on finasteride-induced testicular oxidative stress in Wistar rats

Finasteride used for treating benign prostatic hyperplasia is associated with undesirable side effects via oxidative stress related mechanisms. This study employed in vivo and in silico methods to investigate the protective role of hesperidin against testicular toxicity induced by finasteride and the possible molecular mechanisms involved. Male Wistar rats were randomized into four groups of six animals each. Group I (control) were administered distilled water, group II received finasteride (3.1 mg/kg bw), group III received hesperidin (100 mg/kg bw), while group IV were co-administered finasteride and hesperidin. Administration was by gavage for 14 days. The binding propensities of finasteride and hesperidin for 5 alpha-reductase were assessed using in silico docking approach. Finasteride administration caused significant reductions of sperm motility, volume, count, and live/dead ratio, with significant increase in numbers of abnormal sperms. Finasteride treatment also resulted in diminished activities of superoxide dismutase, catalase and glutathione-S-transferase, significant reduction in the concentration of reduced glutathione and ascorbic acid, and increased testicular malondialdehyde level relative to control. Moreover, significant increase in the activities of testicular lactate dehydrogenase and gamma-glutamyl transferase was observed, with significant decrease in the activities of acid phosphatase and alkaline phosphatase relative to finasteride-treated rats. Furthermore, hesperidin exhibited favorable binding affinity for 5 alpha -reductase (5AR) in silico compared to finasteride. Co-administration with hesperidin ameliorated finasteride-induced testicular damage by suppressing oxidative stress indices, enhancing antioxidant status, improving sperm parameters and alterations in the activities of marker enzymes, as well as possibly inhibiting the binding of finasteride to 5AR.