Silymarin Mitigates Chemotherapy Induced Testicular Injury by Enhancing Antioxidant Defense and Preserving Reproductive Function in Male Mice

OBJECTIVE: To study ameliorative effects of silymarin on hormonal balance, oxidative stress markers, sperm quality and testicular histopathology in male mice exposed to cyclophosphamide (CP). DESIGN: Controlled experimental animal-study. SUBJECTS: Eighty adult male mice were randomly assigned to five groups (N = 16 for each group) as untreated control, CP-only, silymarin (100 mg/kg) + CP, silymarin (200 mg/kg) + CP and last groups as silymarin-only. EXPOSURE: Silymarin was given orally for 28 consecutive days while a single intraperitoneal dose of CP (200 mg/kg) was administered on day 22 to induce testicular injury. MAIN OUTCOME MEASURES: Body and testicular weights were recorded at sacrifice and serum concentrations of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were quantified. Testicular tissues were analyzed for oxidative stress parameters (MDA, SOD, CAT, GSH), sperm-characteristics including (count, motility, morphology) and histopathological change. RESULTS: Cyclophosphamide (CP) showed significantly decreased body and testicular-weights, reduced testosterone levels and impaired sperm-parameters accompanied by rising in MDA and depletion of antioxidant-enzymes along with severe histopathological-changes. Co-administration of silymarin mitigated these adverse effects in a dose-dependent pattern. High-dose silymarin markedly restored hormonal levels, sperm quality, antioxidant balance and normal testicular-architecture to near-control levels. Silymarin alone produced no detrimental effects. CONCLUSION: These results indicate that silymarin mitigates cyclophosphamide-induced testicular toxicity by enhancing antioxidant defenses, stabilizing hormonal function and preserving spermatogenesis in male mice.