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.

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.

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