Doxorubicin-Induced Reproductive Dysfunction in Wistar Rats: Biochemical, Oxidative Stress, Enzymatic and Spermatological Evaluation with Hesperidin Amelioration

Doxorubicin (DOX) is a widely used chemotherapeutic agent whose clinical application is limited by its adverse effects on male reproductive function. The present study was undertaken to evaluate the protective effect of hesperidin against DOX-induced reproductive toxicity in 40 adult male Wistar rats. The rats were randomly allocated to five groups, each of 8 animals, comprising a control group, a DOX-treated group, a DOX plus benazepril group, and DOX plus hesperidin (100 and 200 mg/kg) groups. Treatments were administered for 28 days, after which serum biochemical parameters, testicular oxidative stress markers, lactate dehydrogenase activity and epididymal sperm characteristics were evaluated. Doxorubicin administration caused significant reproductive dysfunction, evidenced by increased serum alkaline phosphatase and testicular malondialdehyde levels, decreased testosterone, superoxide dismutase and testicular LDH activities, and marked deterioration in sperm count, motility, viability and morphology. Co-administration of hesperidin significantly ameliorated these alterations in a dose-dependent manner, with the higher dose (200 mg/kg) restoring most parameters close to normal values and exhibiting greater protective efficacy than benazepril. These findings demonstrate that hesperidin effectively attenuates doxorubicin induced reproductive toxicity through its antioxidant and gonadoprotective actions and may serve as a promising adjunctive agent for preserving male reproductive function during doxorubicin-based chemotherapy.