Protective effects of curcumin against methotrexate-induced testicular damage in rats by suppression of the p38-MAPK and nuclear factor-kappa B pathways

Abstract

Objective: Methotrexate (MTX), is a commonly used chemotherapeutic agent. This study aimed to investigate the possibility that curcumin (CMN) protects against MTX-induced testicular damage by affecting the phospho (p)-p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways. Methods: Male Wistar albino rats were subdivided into three groups. The control group was given an intragastric (ig) administration of dimethyl sulfoxide (DMSO) daily for 14 days, the MTX group was given a single intraperitoneal (ip) dose of MTX (20 mg/kg) on the 11th day, and the MTX+CMN group was given ig CMN (100 mg/kg/day, dissolved in DMSO) for 14 days and a single ip dose of MTX (20 mg/kg) on the 11th day. Results: The animal weights, the seminiferous tubule diameter, and germinal epithelium height significantly decreased in the MTX group compared to the control group. The testes weight and the ratio of the testes to body weight did not change, whereas the number of seminiferous tubules and the interstitial space width increased significantly in the MTX group. The number of phospho-p38 (p-p38) MAPK immunopositive cells and the immunoreactivity of NF-kB also increased in the MTX group compared to the control group. Conclusion: CMN prevented the MTX-induced decreases in the body weight, seminiferous tubule diameter, and the germinal epithelium height, while significantly reducing the number of histologically damaged seminiferous tubules and the interstitial space width changes due to MTX. CMN also reduced the number of p-p38 MAPK immunopositive cells and the NF-kB immunoreactivity.