Investigation of the protective and therapeutic effects of silymarin on cyclophosphamide-induced testicular damage

Introduction and objective: Silymarin, a flavonoid derived from the plant milk thistle (Silybum marianum), is a potent antioxidant that protects against free oxygen radicals. Its antioxidant and anti-inflammatory effects have been demonstrated in both human and animal models. Cyclophosphamide (CYP), a member of the alkylating agents group, is an immunosuppressive and anticancer drug. It has been shown that men undergoing CYP regimens experience increased incidence of testicular atrophy, infertility, and azoospermia. The aim of this study is to investigate the protective and therapeutic effects of silymarin on testicular tissue in a cyclophosphamide-induced testicular damage model in rats, using biochemical markers and histopathological outcomes. Materials and Methods: A total of 47 male Wistar-Albino rats were used in this study. The study was planned with one control group consisting of 5 rats and six experimental groups, each comprising 7 rats. Cyclophosphamide was administered as a single intraperitoneal dose, while silymarin (SMN) was given twice daily via oral gavage. At the end of day 14, the rats were sacrificed. Measurements included serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, total antioxidant capacity (TAS), total oxidative capacity (TOS), and malondialdehyde (MDA) activity. The right testis was used for histopathological examination, while the left testis was used for TAS, TOS, and MDA activity measurements. For histological analysis, Hematoxylin-Eosin and Gomori Trichrome staining were performed. Testicular damage was evaluated using Johnsen's scoring system. Results: According to the analysis results, no significant differences were observed between the groups in testicular weight, weight index, and volume. Regarding weight changes in the subjects, it was noted that silymarin (SMN), when administered as a protective agent, significantly reduced weight loss but did not restore it to normal levels. The use of SMN as both a protective and therapeutic agent was found to significantly reduce the oxidative stress index. No significant differences were observed in serum and tissue malondialdehyde (MDA) levels. Silymarin was shown to be effective in maintaining hormonal balance. Conclusion: Our study demonstrated that silymarin provided histopathological and biochemical improvement in cyclophosphamide-induced testicular damage. Furthermore, the therapeutic effect of silymarin in preventing testicular damage was found to be more potent than its protective effect, with higher doses correlating with an increased rate of recovery. Future randomized prospective studies will be instrumental in guiding the use of silymarin for the prevention and treatment of testicular damage, particularly in preserving fertility.. Keywords: Cyclophosphamide, silymarin, testicular damage