Yavuz, Arzu; Uzel, Kemine; Sezgin, Esra Tuba; Paltacı, Şeyma İlayda; Demir, Özlem; Kuzucu, Mehmet; Süleyman, Halis

Background: Ovarian ischemia–reperfusion (I/R) injury is associated with oxidative stress, inflammation, and histopathological damage. The aim of this study was to investigate the potential protective effects of flunarizine against ovarian I/R–induced injury in an experimental rat model. Methods: Rats were divided into four groups: healthy control (HG), sham-operated (SOG), ovarian ischemia–reperfusion (OIR), and flunarizine-treated OIR (FOIR). Ovarian tissues were analyzed in terms of oxidative stress markers, antioxidant enzyme activities, inflammatory cytokines, and histopathological alterations, including follicle counting. Results: Ovarian I/R significantly increased tissue levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) while significantly decreasing total glutathione (tGSH), superoxide dismutase (SOD) and catalase (CAT) levels. Histopathological evaluation revealed severe follicular degeneration, interstitial edema, vascular congestion, and inflammatory cell infiltration in the OIR group. Following flunarizine administration, these biochemical and histopathological alterations were significantly ameliorated, and a partial restoration in follicle counts was observed. Conclusion: The findings of this study demonstrate that flunarizine exerts protective effects against ovarian I/R injury by reducing oxidative stress, inflammation, and histopathological damage.

Hizal, Elif; Uyar, Esra; Bingul, Eda; Cicek, Betul; Demir, Özlem; Mammadov, Renad; Sarigul, Cengiz; Gursul, Cebrail; Suleyman, Halis

Background: Exposure of ovarian tissue to ischaemia and subsequent reperfusion can result in oxidative and inflammatory damage. A decline in adenosine triphosphate (ATP) levels has the potential to initiate pathological processes and compromise antioxidant defence mechanisms. Vigabatrin, an antiepileptic agent, has been shown to increase levels of gamma-aminobutyric acid (GABA). GABA has the potential to increase ATP levels. The present study was conducted to evaluate the preventive effects of vigabatrin concerning ovarian ischaemia-reperfusion (I/R) injury. Methods: The experiment comprised the allocation of thirty female Wistar albino rats into five groups: a sham operation group (SOG), a vigabatrin group (VIG), an ovarian I/R group (OIR), a vigabatrin + sham operation group (VISO), and a vigabatrin + ovarian I/R group (VOIR). Surgical procedures were performed under anesthesia. The VIG and VOIR were given vigabatrin (50 mg/kg, orally). Following a period of anticipation spanning an hour, the ovaries of the SOG, OIR, and VOIR rats were accessed via an abdominal incision. The incision site was sutured without the performance of an I/R procedure on the SOG ovaries. In the OIR and VOIR, the right ovaries were subjected to three hours of ischemia, followed by six days of reperfusion. Drug treatment was administered once a day using the same method for six days. Then, the rats were euthanised with 120 mg/kg ketamine (intraperitoneally). The ovarian tissues were removed. These samples were examined for oxidants, antioxidants, and proinflammatory cytokines. Results: The I/R procedure caused an increase in malondialdehyde, tumour necrosis factor alpha, interleukin 1β, and interleukin 6 levels, as well as a diminish in total glutathione, superoxide dismutase, and catalase in the ovaries, compared to the SOG (p < 0.001). Moreover, in the present study, I/R was found to result in changes in follicle numbers, as well as congestion, dilatation of the vessels, edema, and an increase in inflammatory cells (p < 0.05). In comparison with OIR, VOIR demonstrated a decline in oxidants and proinflammatory cytokines, an augmentation in antioxidants, and a reduction in histopathological damage(p < 0.05). Conclusion: It is proposed that vigabatrin may represent a novel strategy for the prevention of ovarian injury associated with I/R. Clinical trial number: Not applicable.