Prevention of infertility induced by ovarian ischemia reperfusion injury by benidipine in rats: Biochemical, gene expression, histopathological and immunohistochemical evaluation

Introduction: Benidipine has been reported to prevent the ischemia/reperfusion (I/R) damage in heart tissue and to suppress oxidant and proinflammatory cytokine production, increased by I/R. However, There was no information about the effects of benidipine on I/R injury in the ovary and the damage of I/R-induced infertility.

Objectives: The aim of the study was to investigate the effects of benidipine on bilateral ovarian I/R injury and whether or not effective in the treatment of I/R-induced infertility in rats.

Method: Forty-eight females, albino Wistar rats were randomly divided into 4 groups: IRC group (ovarian I/R group, n=12), IRB-2 group (ovarian I/R+2mg/kg benidipine group, n=12), IRB-4 group (ovarian I/R+4mg/kg benidipine group, n=12) and HG group (healthy group with sham operation, n=12). In IRB-2 and IRB-4 groups, two hours ischemia and two hours reperfusion was performed following orally benidipine administration. After this I/R procedure, 6 rats from each group performed bilateral overectomy. Ovarian levels of malondialdehyde (MDA) and total glutathione (tGSH), ovarian gene expressions of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) and also apoptosis were evaluated. The other 6 rats from each group were put in together with six male rats in separated cages for 2 months in order to reproduce. During this period, rats which did not become pregnant were accepted as infertile.

Results: MDA levels, expressions of TNF-α and IL-1β in IRC group were significantly higher than in the SGA group and tGSH was decreased. In total, 4mg/kg benidipine has better prevented ovaries from the increase of oxidants and proinflammatory cytokines, the decrease of antioxidants than 2mg/kg benedipine. In the histopathological examination hemorrhage, congestion, follicle degeneration, neutrophil infiltration and necrosis were seen in ovarian tissue of IRC group. Only dilated and congested blood vessels were found in the IRB-2 group. No histopathological finding was encountered in the IRB-4 group. I/R caused infertility in rats. In total, 4mg/kg benidipine prevented from infertility better than the dose of 2mg/kg benedipine.

Conclusion: In total, 4mg/kg benidipine reduced I/R injury and I/R-related infertility more significantly compared to 2mg/kg benedipine in rat ovaries.