Investigation the effects of adenosine A2A receptor agonist and antagonist on ovarian ischemia-reperfusion injury in rats

Ovarian torsion is one of the most dangerous gynecologic emergencies that is common in women and requires surgery. The lack of specific clinical findings in patients with ovarian torsion leads to delayed diagnosis and treatment. The main pathology that makes tissue damage irreversible in the ovary with torsion is ischemia. When the ovary starts to reperfuse due to detorsion, the risk of ischemia/reperfusion (I/R) injury occurs. In our study, we investigated the relationship between ovarian I/R injury and the selective adenosine A2A receptor agonist Regadenoson and the selective adenosine A2A receptor antagonist Istradefylline and examined whether they mediate their protective effects against ovarian I/R injury at biochemical and histopathological levels. In this study, a total of 80 Wistar albino female rats were used and divided into 10 groups with 8 rats in each group. Additionally, the aim was to demonstrate the effect of the previously unstudied nanoformulation of Istradefylline in ovarian I/R model. Therefore, empty and Istradefylline-loaded nanosuspension formulations were prepared and their images were examined by SEM analysis. Biochemical analyses included NO, MDA, thiol/disulfide balance, 3-NT levels in blood and NO, SOD1, thiol/disulfide balance, 3-NT analysis in tissue. Correlation analyses of the obtained results were performed. The adenosine agonist Regadenoson had decreasing effects on oxidative and nitrosative stress. A significant increase was observed in serum native thiol levels and serum native thiol/total thiol ratio with the administration of a high dose of Regadenoson (P<0.01, P<0.01, respectively). Additionally, Regadenoson was found to reduce serum disulfide levels, serum disulfide/total thiol ratio, serum disulfide/native thiol ratio, serum 3-NT levels, tissue 3-NT levels, and serum NO levels (P<0.05, P<0.001, P<0.01, P<0.05, P<0.05, P<0.05, respectively). This study is the first investigation using Regadenoson and Istradefylline against rat ovarian I/R injury.