Protective effects of ivermectin against ischemia-reperfusion-induced ovarian injury in rats

Abstract

Background Ovarian ischemia-reperfusion (I/R) injury induces severe tissue damage through oxidative stress and inflammation, and DNA damage. This study investigated the protective effects of short- and long-term ivermectin application against ovarian I/R injury in rats. Methods Twenty-four female Wistar albino rats were divided into four groups: sham operation (SOG), ovarian I/R (OIR), long-term ivermectin-applied I/R (LIOIR), and short-term ivermectin-applied I/R (SIOIR). Ovarian torsion was maintained for 3 h before detorsion. Ivermectin (2 mg/kg, orally) was administered for 3 or 6 days. Ovarian malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) were measured. Histopathological and immunohistochemical analyses of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were also performed. Results OIR increased MDA and reduced tGSH, SOD, and CAT. Three-day ivermectin pretreatment normalized oxidative stress marker levels to values comparable to those in the sham group, whereas six-day pretreatment provided no significant protection. Follicular degeneration was pronounced in OIR and LIOIR but markedly attenuated in SIOIR. Immunohistochemistry demonstrated preserved COX-1 expression and reduced COX-2 and 8-OHdG immunoreactivity following short-term ivermectin pretreatment. Conclusion Short-term ivermectin effectively protected ovarian tissue against experimental I/R injury by reducing oxidative stress, inflammation, and DNA damage, whereas prolonged pretreatment failed to provide comparable protection, supporting its therapeutic potential.