The protective effect of JZL184 on ovarian ischemia reperfusion injury and ovarian reserve in rats

Abstract

Ovarian torsion is a gynecopathology that requires emergency surgery in women. However, ischemia reperfusion injury (IRI) occurs after treatment with detorsion. This study aimed to evaluate the effects of monoacylglycerol lipase inhibitor JZL184 on ovarian IRI and ovarian reserve. Forty-eight female Wistar albino rats were divided into six groups. Group 1: Sham, Group 2: Ischemia, Group 3: ischemia/reperfusion (IR), Group 4: IR + JZL184 4 mg/kg, Group 5: IR + JZL184 16 mg/kg, Group 6: IR + vehicle (dimethyl sulfoxide). Three hours of ischemia followed by 3 h of reperfusion. Two different doses of JZL184 (4 and 16 mg/kg) were administered intraperitoneally in Group 4 and 5, 30 min before reperfusion. Ovarian IRI and ovarian reserve were evaluated in serum and tissue by using histopathological and biochemical parameters. Treatment with JZL184 was associated with a significant increase in ovarian 2-arachidonoylglycerol and improved serum anti-Mullerian hormone, İnhibin B, primordial follicle count, and ovarian histopathological damage score (p < 0.05). JZL184 treatment significantly decreased the level of malondialdehyde, and increased superoxide dismutase enzyme activity and glutathione (GSH) levels (p < 0.05). The increased phosphorile nuclear factor-κB (Phospho-NF-κB-p65), tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), transforming growth factor beta 1 (TGF-β1), and TUNEL assay immunopositivity scores in ovarian I/R injury were decreased after treatment with JZL184 (p < 0.05). JZL184 showed significant ameliorative effects on ovarian IRI and ovarian reserve caused by IR through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. Thus, JZL184 may be a novel therapeutic agent for ovarian IRI.