Protective Role of Doxofylline against Cyclophosphamide-induced Testicular Toxicity in Rats

Abstract

Background: Cyclophosphamide (CP) is a widely used anticancer and immunosuppressant drug. However, CP's significant toxicities and adverse effects restrict its clinical use. Doxofylline (DF) is a phosphodiesterase inhibitor that has antioxidant and anti-inflammatory properties. Objective: To determine the protective effect of doxofylline on rats exposed to a single dose of CP. Methods: We randomly assigned thirty Sprague-Dawley male rats to three groups. On the sixth day, the apparently healthy control group (AH) received normal saline; the induction group (IN) received normal saline and a single dose of CP (100 mg/kg); and the DF group received DF (50 mg/kg) and a single dose of CP (100 mg/kg). Treatment in all groups was given once daily and intraperitoneally. At the end of treatment, caudal fluid is used to determine sperm parameters. A blood sample was taken to determine the testosterone levels. We determined the levels of testicular glutathione peroxidase and malondialdehyde. The testes were harvested, allowing for histological examination. Results: Sperm parameters, testosterone and oxidative stress markers were notably declining in testicular tissue among the IN compared with AH, although these measures can be markedly improved with DF. Histopathological analysis revealed a substantial change in the testicular tissue structure in the CP group, although doxofylline co-treatment significantly attenuated and even reversed these changes. Conclusions: Doxofylline may function as a protective agent, mitigating the testicular damage caused by CP therapy in rats. The proposed process may be attributed to its phosphodiesterase inhibitory and antioxidant properties.