# Contribution of adenosine A2A receptor agonist and antagonist on ovarian ischemia/reperfusion injury in rats

## TL;DR

This study examines how adenosine A2A receptor agonist and antagonist affect ovarian injury in rats caused by ischemia and reperfusion.

## Contribution

The novel contribution is evaluating the protective effects of regadenoson and istradefylline in ovarian ischemia/reperfusion injury using a rat model.

## Key findings

- Regadenoson reduced oxidative stress markers like malondialdehyde and 3-nitrotyrosine in ovarian tissue.
- Istradefylline and its nanosuspension increased superoxide dismutase levels, indicating antioxidant effects.
- Regadenoson prevented decreases in native thiol levels and suppressed increases in disulfide levels caused by ischemia/reperfusion.

## Abstract

To determine the effects of an A2A receptor agonist regadenoson, an A2A receptor antagonist istradefylline, and istradefylline nanosuspension on ovarian ischemia/reperfusion (I/R) injury in rats.

A total of 80 female rats were divided into 10 groups: sham, ovarian I/R, blank nanosuspension + ovarian I/R, regadenoson (3 μg/kg) + ovarian I/R, regadenoson (30 μg/kg) + ovarian I/R, istradefylline (0.3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + ovarian I/R, istradefylline-loaded nanosuspension (3 mg/kg) + ovarian I/R, istradefylline (3 mg/kg) + regadenoson (30 μg/kg) + ovarian I/R, and istradefylline-loaded nanosuspension (3 mg/kg) + regadenoson (30 μg/kg) + ovarian I/R. ELISA, chemiluminescence, and spectrophotometric analyses were performed on blood and ovarian tissue samples. Histopathological changes were analyzed using hematoxylin and eosin staining, and a scoring system was applied to assess ovarian tissue damage.

Serum malondialdehyde levels were augmented in the I/R and blank nanosuspension + I/R groups. Although tissue superoxide dismutase levels were decreased with I/R, these levels were increased with regadenoson (3 μg/kg), istradefylline (0.3–3 mg/kg), and istradefylline nanosuspension (3 mg/kg). While there was augmentation in the serum and tissue 3-nitrotyrosine levels in the I/R group, a marked decrease was identified with regadenoson (30 μg/kg, p < 0.05). Native thiol levels were decreased in the I/R group, and this decrease was prevented by regadenoson. Serum disulfide levels were increased in the I/R group, and this increase was suppressed by regadenoson.

These data showed that adenosine A2A receptors may contribute to the ovarian I/R injury and regadenoson can produce protective effects.