Erythropoietin Protective Role Against Methotrexate Testicular Adverse Effects

Abstract

Background: The adverse effects of cytotoxic medications like methotrexate, particularly reproductive damage reported in the numerous experimental studies, limit their effectiveness as anticancer therapies. The current study's objectives were to identify potential histological and immune-histochemical unfavorable changes in the testicles due to methotrexate medication and to assess any possible protective effects of erythropoietin (EPO). Methods and Results: The study included 60 mature male albino rats weighing 200-250g. The animals were divided equally into three groups, each with 20 rats. In Group 1, the control group, the animals received intraperitoneal injections of normal saline twice a week for nine weeks at a dose of 0.5 mg/kg. For nine weeks, animals in Group 2 received intraperitoneal injections of methotrexate hydrate at 0.5 mg/kg twice a week. Animals in Group 3 received subcutaneous injections of 100 IU/kg recombinant human EPO once a week for nine weeks and intraperitoneal injections of methotrexate hydrate at a dosage of 0.5 mg/kg twice a week for nine weeks. Each rat was weighed every week throughout the examinations. An ELISA technique was used to measure the levels of testosterone, malondialdehyde (MDA), total antioxidant capacity (TAC), and ROS in blood serum. Morphological and histopathological changes in testicular tissue were assessed. The body weight in the rats treated with methotrexate was considerably lower than in control group rats. EPO showed clear androgenic and antioxidant activities and reduced the adverse effects of methotrexate on testicular histology. Our results suggest further research into the use of EPO as a drug to protect patients from the adverse effects of methotrexate.

Keywords

• testicular tissue
• erythropoietin
• methotrexate
• oxidative stress