Effects of Riociguat on Ovarian Ischemia–Reperfusion Injury: Modulation of Oxidative Stress, Inflammation, and Endocrine Function in a Rat Model
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Background: Ovarian torsion is a gynecological emergency in which ischemia and reperfusion cause tissue damage through oxidative stress and microvascular dysfunction. Riociguat, a soluble guanylate cyclase (sGC) stimulator, enhances cyclic guanosine monophosphate (cGMP) production and may protect against ischemia-reperfusion (I/R) injury. This study evaluated the effects of riociguat on ovarian I/R injury in rats. Methods: Forty-seven Wistar albino rats were randomly assigned to six groups: Control, Sham, Ischemia, I/R, and I/R treated with riociguat at 3 mg/kg (IRR-3) or 10 mg/kg (IRR-10). Ovarian ischemia was induced by adnexal compression for 3 hours followed by 3 hours of reperfusion. Riociguat was administered orally at the 90th minute of ischemia. Oxidative stress, hormonal, inflammatory, histopathological, and immunohistochemical parameters were evaluated. Statistical significance was set at p < 0.05. Results: TBARS levels increased after ischemia and I/R ( p < 0.001) and decreased following riociguat treatment ( p < 0.05). GSH levels differed among groups ( p < 0.001), with the highest levels in the IRR-10 group ( p < 0.05). Serum LH levels were highest in the I/R group ( p < 0.001) and decreased after riociguat treatment ( p < 0.05). FSH levels were higher in the IRR-10 group than in the ischemia, I/R, and IRR-3 groups ( p < 0.05). Estradiol levels decreased after ischemia and I/R ( p < 0.05) but increased following IRR-10 treatment ( p < 0.05). IL-10 levels increased in the IRR-10 group compared with the ischemia group ( p = 0.001). Histopathological analysis showed increased vascular congestion ( p < 0.001), edema, hemorrhage, and follicular degeneration ( p < 0.05), whereas necrosis increased only in the IRR-3 group ( p = 0.049). eNOS expression was lower in the IRR-10 group than in the ischemia group ( p = 0.0013). Conclusions: Riociguat reduced oxidative stress ( p < 0.05), enhanced antioxidant capacity ( p < 0.001), improved endocrine function ( p < 0.05), and promoted anti-inflammatory responses ( p = 0.001), providing partial protection against ovarian I/R injury. Although these findings are consistent with sGC stimulation, direct activation of the NO–sGC–cGMP pathway was not demonstrated.
