Protective effect of infliximab on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation Remzi Abali a, *, Nicel Tasdemir a , Mehmet Aytac Yuksel b , Savas Guzel c , Meltem Oznur d , Burcin Nalbantoglu e , Ufuk Goker Tasdemir f a Namik Kemal University, Faculty of Medicine, Department of Gynecology and Obstetrics, Tekirdag, Turkey b I ˙ stanbul University, Cerrahpasa Faculty of Medicine, Department of Gynecology and Obstetrics, Istanbul, Turkey c Namik Kemal University, Faculty of Medicine, Department of Biochemistry, Tekirdag, Turkey d Namik Kemal University, Faculty of Medicine, Department of Pathology, Tekirdag, Turkey e Namik Kemal University, Faculty of Medicine, Department of Pediatrics, Tekirdag, Turkey f Hayrabolu State Hospital, Tekirdag, Turkey 1. Introduction Adnexal torsion is a gynecological emergency with a prevalence of 2.7% [1]. Early diagnosis and management are crucial for the preservation of ovarian function. In general, the management modality of patients, especially at younger ages, to preserve fertility is detorsion rather than removal of adnexa. Detorsion, however, leads to neutrophil infiltration and excessive production of reactive oxygen species [2]. The oxidative distress occurring with the reperfusion of the ischemic tissue is called ‘‘ischemia/ reperfusion injury’’ (IRi) [2]. Inflammatory mechanisms are also important in the pathogenesis of IRi. Various inflammatory mediators were described contributing to IRi, such as leukocytes, adhesion molecules and cytokines [3]. Tumor necrosing factor alpha (TNFa) is the primary mediator of inflammation during IRi [4]. Thus, we hypothesized that the application of TNFa antagonists would result in decreased IRi. Infliximab (Remicade, Schering- Plough, Berlin) is a chimeric monoclonal antibody for TNFa, and binds both transmembrane and soluble forms of TNFa. It is approved for treatment of inflammatory diseases. To the best of our knowledge, this is the first study investigating possible effects of a TNFa antagonist on IRi of ovarian tissues due to ovarian torsion. We designed a rat model including various torsion and reperfusion models to test our hypothesis. European Journal of Obstetrics & Gynecology and Reproductive Biology 171 (2013) 353–357 ARTICLE INFO Article history: Received 19 June 2013 Received in revised form 21 August 2013 Accepted 29 September 2013 Keywords: Tumor necrosing factor alpha antagonist Infliximab Ovarian torsion Ischemia Reperfusion Rat ABSTRACT Objective: The aim of this study was to investigate the effect of infliximab on experimentally induced ovarian ischemia/reperfusion injury (IRi). Study design: A total of 42 female rats were equally divided into 6 experimental groups; group 1: sham operation, group 2: 3-h ischemia, group 3 and 4: 3-h ischemia, 3-h reperfusion, group 5 and 6: 3-h ischemia, 24 h reperfusion. In group 4 and group 6, 30 min before reperfusion, infliximab was administered intraperitoneally at a dose of 5 mg/kg. Bilateral ovaries were removed for histopathologic and biochemical analysis. Serum MDA (sMDA), tissue MDA (tMDA), serum NO (sNO), tissue NO (tNO) and serum catalase concentrations were analyzed. Tissue damage of ovarian tissue was scored by histological examination. Results: The infliximab administration significantly lowered the sNO, tNO and sMDA concentrations in group 4 compared to group 3 (p = 0.041, p = 0.025 and p = 0.035, respectively). sNO, tNO and sMDA concentrations were also lower in group 6 when compared to group 5, but this differences were not significant (p > 0.05). On the other hand, tMDA concentrations were lower in infliximab-applied groups when compared to ischemia/reperfusion groups (group 3 vs. 4 and 5 vs. 6) (p = 0.045 and p = 0.048, respectively). Moreover, histopathologic tissue damage scores in infliximab administration groups were significantly lower than in ischemia/reperfusion groups (p < 0.001). Conclusion: Infliximab attenuates I/R-induced ovarian tissue injury in rats subjected to ischemia/ reperfusion. ß 2013 Elsevier Ireland Ltd. All rights reserved. * Corresponding author at: Namik Kemal University, Faculty of Medicine, Department of Gynecology and Obstetrics, 100. Yil Mah. Barbaros Cad, No: 132, Tekirdag, Turkey. Tel.: +90 282 2620130/532 7315360; fax: +90 282 2626810. E-mail addresses: remziabali@yahoo.com, rabali@nku.edu.tr (R. Abali). Contents lists available at ScienceDirect European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb 0301-2115/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejogrb.2013.09.037