Silymarin mitigates chemotherapy-induced testicular injury by enhancing antioxidant defense and preserving reproductive function in male mice

Abstract

Objective

To study the ameliorative effects of silymarin on hormonal balance, oxidative stress markers, sperm quality, and testicular histopathology in male mice exposed to cyclophosphamide (CP).

Design

This is a controlled experimental animal study.

Subjects

Eighty adult male mice were randomly assigned to 5 groups (N = 16 for each group) as untreated control, CP only, silymarin (100 mg/kg) + CP, silymarin (200 mg/kg) + CP, and 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, and follicle-stimulating hormone were quantified. Testicular tissues were analyzed for oxidative stress parameters (malondialdehyde, superoxide dismutase, catalase, and reduced glutathione), sperm characteristics including count, motility, morphology, and histopathological changes.

Results

Cyclophosphamide showed significantly decreased body and testicular weights, reduced testosterone levels, and impaired sperm parameters, accompanied by a rise in malondialdehyde and depletion of antioxidant enzymes along with severe histopathological changes. Co-administration of silymarin mitigated these adverse effects in a dose-dependent manner. 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 CP-induced testicular toxicity by enhancing antioxidant defenses, stabilizing hormonal function, and preserving spermatogenesis in male mice.