Protective Effects of Ranolazine in a Rat Model of Ovarian Ischemia/Reperfusion Injury

Abstract

Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion.