The Effect of Captopril and Losartan on Tacrolimus-Induced Testicular Toxicity in Rats

Abstract

Background: Tacrolimus is an immunosuppressive drug broadly used to avoid rejection of tissue transplantation. Some studies suggest that tacrolimus has destructive effects on the male reproductive system due to activation of the renin-angiotensin system (RAS) and inflammation. Objectives: The present study aimed at determining the toxic effects of tacrolimus on testis and evaluating the blocking effects of captopril and losartan on angiotensin-converting enzyme (ACE) and angiotensin receptors, respectively, in rats. Methods: The present experimental study was conducted on 36 adult male Wistar rats (weighing 200 ± 20 g) randomly divided into six groups and treated based on the experimental design for 30 days. At the end of the intervention, the rats were anesthetized and their blood samples were obtained to measure the serum levels of testosterone and ACE2 enzyme. Also, both testes were removed for histopathological examinations after scarifying. Results: Tacrolimus decreased testosterone and ACE2 levels significantly. The ACE2 levels were lower in the groups treated with a combination of tacrolimus and losartan or captopril compared to the control group while testosterone level significantly increased in the groups receiving a combination of tacrolimus and captopril. The epithelial thickness of seminiferous tubules and the number of primary spermatocytes significantly decreased in the rats only receiving tacrolimus compared to the groups that received captopril and losartan, along with tacrolimus. Conclusions: According to the findings, the administration of captopril or losartan, along with tacrolimus, can decrease its testicular toxicity. Captopril and losartan act through blocking RAS but cannot improve ACE2 level; therefore, the recovery of testicle tissue might not be attributed to the ACE2 approach but to the anti-inflammatory effect.