Aim: To study the detrimental effects of cyclophosphamide on the testicular androgenic and gametogenic activities through endocrine inhibition and/or induction of oxidative stress in male albino rats and to evaluate the protective effect of ascorbic acid. Methods: The testicular D5, 3b-hydroxysteroid dehydrogenase (HSD), 17b-HSD, peroxidase and catalase activities along with the levels of malondialdehyde (MDA) and conjugated dienes in testicular tissue were measured for the evaluation of testicular oxidative stress. The plasma testosterone (T) level was measured by immunoassay. Various germ cells at stage VII of spermatogenic cycle were quantified from testicular stained sections. Results: Cyclophosphamide treatment results in a significant inhibition in the testicular D5, 3b-HSD and 17b-HSD activities, a decrease in plasma T level and a diminution in the counts of various germ cells. Moreover, this treatment was also associated with a significant inhibition of the peroxidase and catalase activities along with high levels of MDA and conjugated dienes in the testis. All these changes were reversed by ascorbic acid co-administration. Conclusion: Cyclophosphamide treatment at the dosage used caused testicular gametogenic and androgenic disorders as well as induced testicular oxidative stress that can be reversed by ascorbic acid co-administration

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