Protective Effects of Prophylactic and Therapeutic Erythromycin Administration in Ovarian Ischemia–Reperfusion Injury in Rats

Background and Objectives: Ovarian ischemia–reperfusion (I/R) injury involves oxidative stress, inflammation, and structural tissue damage that may impair ovarian function. This study investigated the effects of prophylactic and therapeutic erythromycin administration on biochemical and histopathological injury in a rat model of ovarian I/R. Materials and Methods: Forty adult female Wistar albino rats were divided into five groups (n = 8 per group): sham (SG), I/R, erythromycin alone (E), prophylactic erythromycin plus I/R (I/R+ERP), and therapeutic erythromycin plus I/R (I/R+ERT). Ovarian ischemia was induced by clamping the right ovarian vascular pedicle for 3 h, followed by 3 h of reperfusion. Erythromycin (50 mg/kg, intraperitoneally) was administered 30 min before ischemia in the I/R+ERP group and at the onset of reperfusion in the I/R+ERT group. Inflammatory and oxidative stress markers in serum and ovarian tissue, serum anti-Müllerian hormone (AMH) levels, and ovarian hemorrhage and necrosis were evaluated. Results: Compared with the sham group, ovarian I/R increased inflammatory and oxidative stress markers and histopathological injury, and decreased serum AMH and ovarian tissue glutathione (GSH) and superoxide dismutase (SOD) levels. Compared with the untreated I/R group, both erythromycin regimens were associated with lower serum and ovarian tissue tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels and lower ovarian necrosis scores. The I/R+ERT group also had lower ovarian tissue interleukin-1β (IL-1β), higher ovarian tissue GSH and SOD levels, and a lower hemorrhage score than the untreated I/R group. In the direct comparison between the two erythromycin regimens, serum MDA was lower (false discovery rate [FDR]-adjusted q < 0.001), ovarian tissue SOD was higher (q = 0.014), and the ovarian necrosis score was lower (Holm-adjusted p < 0.001) in the I/R+ERT group. Direct comparisons for serum TNF-α (q = 0.055), ovarian tissue IL-1β (q = 0.127), and ovarian tissue GSH (q = 0.105) did not meet the FDR-adjusted significance threshold. The hemorrhage score did not differ significantly between the two erythromycin regimens (Holm-adjusted p = 0.057). Neither regimen significantly increased serum AMH compared with the untreated I/R group. Conclusions: Erythromycin attenuated several biochemical and histopathological indicators of acute experimental ovarian I/R injury. Administration at the onset of reperfusion was associated with more favorable findings than prophylactic administration for selected outcomes. These short-term findings do not establish preservation of ovarian reserve or fertility, or clinical efficacy in ovarian torsion.