Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress
Authors: Elsaeed Magdy Y. , Mehanna Osama Mahmoud , Abd-Allah Ezz-Eldin El-Sharkawy , Hassan Mohamed G. M. , Ahmed Walid Mostafa Said , Moustafa Abd El Ghany , Eldesoky Gaber E. , Hammad Amal Mahmoud , Elgazzar Usama Bahgat , Elnady Mohamed Ramadn , AbdAllah Fatma , Shipl Walaa Mohammed , Amer Ahmed Elsayed , Younes Amr Mohamed , Magar Mostafa Rizk , Abbas Mohamed Ali Mahmoud , Elhamaky Kkaled Saleh Ali , Hassan Mohammed Hussien Mohammed 
Published: October 2023

Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in an urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The purpose of this study was to assess the protective impact of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analogue) alone and in combination, on streptozotocin (STZ) diabetes-induced testicular dysfunction in rats.

Material and methods: This study was carried on 50 male Sprague-Dawley rats; 10 normal rats were allocated as non-diabetic control group. 40 rats developed diabetes after receiving a single dose of STZ, then the diabetic rats were divided into four groups of equivalent number assigned as diabetic control, enalapril treated, paricalcitol treated, in addition to combined enalapril and paricalcitol treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress and inflammatory parameters as well as histopathological examination were assessed when compared to the normal and diabetic control rats.

Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle stimulating hormone (FSH) as well as luteinizing hormone (LH) and the antioxidant enzyme activities were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6) as well as tumor necrosis factor-α (TNF-α) were significantly increased, along with sever distortion of testicular structure. Interestingly, treatment with paricalcitol and enalapril either alone or in combination significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH and LH, reduced insulin resistance, IL-6 and TNF-α levels and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs than monotherapy with enalapril alone.

Conclusion: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving the diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory and anti-apoptotic properties), than monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.