PROTECTIVE EFFECT OF DAPANSUTRILE AGAINST METHOTREXATE-INDUCED TESTICULAR TOXICITY IN RATS

Background: Methotrexate (MTX) is a widely used therapy for the treatment of malignancies and autoimmune diseases; however, its use is limited by adverse effects such as testicular toxicity and impairment of male fertility. Objective: This study aimed to evaluate the protective effect of dapansutrile (DAPA) against methotrexate (MTX)-induced testicular toxicity in rats. Methods: Twenty-four adult male rats were divided into four groups: control, MTX, MTX + DAPA (10 mg/kg), and MTX + DAPA (20 mg/kg). Testicular toxicity was first assessed by measuring relative testicular weight, sperm count, and sperm viability, in addition to histopathological examination of testicular tissue. Results: Administration of MTX resulted in a non-significant decrease in relative testicular weight; however, it caused a significant reduction in sperm count and viability. In addition, marked histopathological alterations were observed, including degeneration of seminiferous tubules and disruption of spermatogenesis. Co-administration of DAPA with MTX produced a mild, dose-dependent improvement, where DAPA-treated groups showed a significant recovery in sperm parameters and partial restoration of testicular histoarchitecture. Conclusion: DAPA effectively attenuated MTX-induced testicular toxicity, preserving both testicular structure and function in a mild, dose-dependent manner. These findings suggest its potential role as a protective agent against chemotherapy-induced reproductive toxicity.