TY - JOUR T1 - Ovarian Ischemia-Reperfusion Injury and the Potential Role of Mangiferin: A Histopathological, Biochemical Investigation TT - Over İskemi-Reperfüzyon Hasarı ve Mangiferin’in Olası Rolü: Histopatolojik ve Biyokimyasal Bir İnceleme AU - Ayaz, Hayat AU - Aşır, Fırat PY - 2025 DA - September Y2 - 2025 DO - 10.30934/kusbed.1730683 JF - Kocaeli Üniversitesi Sağlık Bilimleri Dergisi JO - KOU Sag Bil Derg PB - Kocaeli Üniversitesi WT - DergiPark SN - 2149-8571 SP - 160 EP - 166 VL - 11 IS - 3 LA - en AB - Objective: Ischemia-reperfusion (IR) injury in the ovary can cause significant structural damage and compromise ovarian reserve by disrupting follicular integrity. This study aimed to investigate the protective effects of Mangiferin, a natural antioxidant and anti-inflammatory compound, in a rat model of ovarian IR injury. Histopathological evaluation, follicle counts, and serum anti-Müllerian hormone (AMH) levels were used to assess treatment efficacy.Methods: Thirty-two female Sprague-Dawley rats were divided into Control, Mangiferin, IR, and IR+ Mangiferin. Ovarian IR was induced by bilateral clamping of the ovarian vasculature for 3 hours, followed by 3 hours of reperfusion. Mangiferin (20 mg/kg) was administered intraperitoneally once daily for 15 days. Ovarian tissues were subjected to histological analysis with follicle counts and AMH levels were measured using ELISA.Results: The IR group exhibited marked histopathological changes, including vascular congestion, hemorrhage, edema, inflammatory cell infiltration, and extensive follicular degeneration. In contrast, the IR+ Mangiferin group showed improved tissue architecture, higher follicle counts, and AMH levels that were significantly preserved compared to the IR group. Conclusion: Mangiferin may reduce ovarian damage caused by IR injury and contribute to the preservation of ovarian reserve. These findings suggest a potential therapeutic benefit of Mangiferin in protecting ovarian tissue under ischemic conditions. KW - Anti Müllerian Hormone KW - Histopathology KW - İschemia Reperfusion İnjury KW - Mangiferin KW - Ovary N2 - Amaç: Overde gelişen iskemi-reperfüzyon (IR) hasarı, folikül bütünlüğünü bozarak belirgin doku hasarına ve over rezervinin azalmasına yol açabilir. Bu çalışmada, Mangiferin’in IR kaynaklı over hasarına karşı olası koruyucu etkilerinin; histopatolojik değişiklikler, folikül sayısı ve serum Anti-Müllerian Hormon (AMH) düzeyleri üzerinden değerlendirilmesi amaçlanmıştır.Yöntem: Otuz iki dişi Sprague-Dawley sıçan dört gruba ayrılmıştır: Kontrol, Mangiferin, IR ve IR+Mangiferin. Over IR modeli, bilateral over vaskülatürünün üç saat süreyle kleplenmesi ve ardından üç saatlik reperfüzyon uygulanması ile oluşturulmuştur. Mangiferin (20 mg/kg), 15 gün boyunca intraperitoneal yolla günde bir kez uygulanmıştır. Over dokuları histopatolojik incelemeye tabi tutulmuş; folikül sayımları gerçekleştirilmiş ve serum AMH düzeyleri ELISA yöntemiyle analiz edilmiştir.Bulgular: IR grubunda vasküler konjesyon, hemoraji, ödem, inflamatuar hücre infiltrasyonu ve belirgin folikül dejenerasyonu gibi ciddi histopatolojik bozulmalar gözlemlenmiştir. Buna karşın, IR+Mangiferin grubunda over dokusunun histolojik bütünlüğünün korunduğu, folikül sayılarının daha yüksek olduğu ve AMH düzeylerinin göreceli olarak korunduğu saptanmıştır.Sonuç: Mangiferin, IR kaynaklı over hasarını azaltabilir ve over rezervinin korunmasına katkı sağlayabilir. Bulgular, Mangiferin’in iskemik koşullarda over dokusunu korumaya yönelik potansiyel bir tedavi ajanı olabileceğini göstermektedir. CR - Williams CJ, Erickson GF. Morphology and physiology of the ovary. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. Updated April 24, 2025. Accessed April 24, 2025. https://www.ncbi.nlm.nih.gov/books/NBK278951/ CR - Demir Çaltekin M, Özkut MM, Çaltekin İ, et al. The protective effect of JZL184 on ovarian ischemia reperfusion injury and ovarian reserve in rats. J Obstet Gynaecol Res. 2021;47(8):2692-2704. doi:10.1111/jog.14859 CR - Deniz E, Topcu A, Ozturk A, et al. The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation. Int Immunopharmacol. 2022;107:108676. doi:10.1016/j.intimp.2022.108676 CR - Kölükçü V, Balta MG, Tapar H, et al. Etomidate alleviates ovarian ischemia-reperfusion injury in rats. Ulus Travma Acil Cerrahi Derg. 2024;30(6):375-381. doi:10.14744/tjtes.2024.27388 CR - Kula H, İlgen O, Kurt S, Yılmaz F. Effects of allium cepa on ovarian torsion-detorsion injury in a rat model. Turk J Obstet Gynecol. 2023;20(2):137. doi:10.4274/tjod.galenos.2023.41763 CR - Uzel K, Lakhno I, Turkler C, et al. Tocilizumab is effective in preventing ovarian injury induced by ischemia-reperfusion in rats. An Acad Bras Cienc. 2023;95(1):e20220442. doi:10.1590/0001-3765202320220442 CR - Öztürk AB, Akaras N, Şimşek H, Kandemir FM. Investigation of the effects of silymarin on ovarian ischemia reperfusion via Nrf-2/HO-1/NQO1, Ki-67 and Wnt signaling pathways. J Biochem Mol Toxicol. 2025;39(1):e70138. doi:10.1002/jbt.70138 CR - Ayaz H, Aşır F, Korak T. Skimmianine showed neuroprotection against cerebral ischemia/reperfusion injury. Curr Issues Mol Biol. 2024;46:7373-7385. doi:10.3390/cimb46070437 CR - Tunç N, Tas M, Görük M, Kirman G, Deveci E. Effects of Potentilla fulgens as prophylactic agent in intestinal ischemia reperfusion injury. Int J Morphol. 2015;33:1313-1318. doi:10.4067/S0717-95022015000400020 CR - Karateke F, Karateke A, Topdagi B, et al. The role of mannitol and vitamin D in ovarian ischemia/reperfusion injury in rats with acute abdominal. Curr Issues Mol Biol. 2024;46(8):8903-8913. doi:10.3390/cimb46080526 CR - Arslan S, Aşır F, Özkorkmaz EG, et al. Protective effects of Passiflora incarnata on ovarian ischemia/reperfusion damage in rats with ovarian torsion. Ulus Travma Acil Cerrahi Derg. 2023;29(12):1344-1350. doi:10.14744/tjtes.2023.52986 CR - Karaman E, Onder GO, Goktepe O, et al. Protective effects of boric acid taken in different ways on experimental ovarian ischemia and reperfusion. Biol Trace Elem Res. 2024;202(6):2730-2743. doi:10.1007/s12011-023-03871-1 CR - Eken MK, Ersoy GS, Kaygusuz EI, et al. Etanercept protects ovarian reserve against ischemia/reperfusion injury in a rat model. Arch Med Sci. 2019;15(4):1104-1112. doi:10.5114/aoms.2017.72406 CR - Yilmaz F, Ilgen O, Mankan A, et al. The effects of berberine on ischemia-reperfusion injuries in an experimental model of ovarian torsion. Clin Exp Reprod Med. 2023;50(4):292-298. doi:10.5653/cerm.2023.06366 CR - Ulusoy Tangul S, Onat T, Aydoğan Kirmizi D, et al. Effect of bromelain on ischemia-reperfusion injury in the torsion model created in polycystic and normal ovarian tissues. Front Pharmacol. 2024;15:1451592. doi:10.3389/fphar.2024.1451592 CR - Mete Ural Ü, Bayoğlu Tekin Y, Şehitoğlu İ, et al. Biochemical, histopathological and immunohistochemical evaluation of the protective and therapeutic effects of thymoquinone against ischemia and ischemia/reperfusion injury in the rat ovary. Gynecol Obstet Invest. 2016;81(1):47-53. doi:10.1159/000431220 CR - Değer U, Çavuş Y. Investigation of the role of rosmarinic acid treatment in regulating inflammation, cell damage, and angiogenesis in rat ovarian torsion and detorsion models. Acta Cir Bras. 2020;35(3):e202000304. doi:10.1590/s0102-865020200030000004 CR - Du S, Liu H, Lei T, et al. Mangiferin: An effective therapeutic agent against several disorders (review). Mol Med Rep. 2018;18(6):4775-4786. doi:10.3892/mmr.2018.9529 CR - Zhang H, Wang L, Wang X, et al. Mangiferin alleviated poststroke cognitive impairment by modulating lipid metabolism in cerebral ischemia/reperfusion rats. Eur J Pharmacol. 2024;977:176724. doi:10.1016/j.ejphar.2024.176724 CR - Liu K, Wang F, Wang S, et al. Mangiferin attenuates myocardial ischemia-reperfusion injury via MAPK/Nrf-2/HO-1/NF-κB in vitro and in vivo. Oxid Med Cell Longev. 2019;2019:7285434. doi:10.1155/2019/7285434 CR - Gendy AM, El-Gazar AA, Ragab GM, et al. Possible implication of Nrf2, PPAR-γ and MAPKs signaling in the protective role of mangiferin against renal ischemia/reperfusion in rats. Pharmaceuticals. 2023;16(1):6. doi:10.3390/ph16010006 CR - El-Sayyad SM, Soubh AA, Awad AS, El-Abhar HS. Mangiferin protects against intestinal ischemia/reperfusion-induced liver injury: involvement of PPAR-γ, GSK-3β and Wnt/β-catenin pathway. Eur J Pharmacol. 2017;809:80-86. doi:10.1016/j.ejphar.2017.05.021 CR - Islam MR, Ichii O, Nakamura T, et al. Comparison of ovarian morphology and follicular disturbances between two inbred strains of cotton rats (Sigmodon hispidus). Animals. 2021;11(6):1768. doi:10.3390/ani11061768 CR - Moolhuijsen LME, Visser JA. Anti-Müllerian hormone and ovarian reserve: update on assessing ovarian function. J Clin Endocrinol Metab. 2020;105(11):3361-3373. doi:10.1210/clinem/dgaa513 CR - Wang B, Wan J, Gong X, et al. Mangiferin attenuates renal ischemia-reperfusion injury by inhibiting inflammation and inducing adenosine production. Int Immunopharmacol. 2015;25(1):148-154. doi:10.1016/j.intimp.2014.11.011 CR - Mahmoud-Awny M, Attia AS, Abd-Ellah MF, El-Abhar HS. Mangiferin mitigates gastric ulcer in ischemia/reperfused rats: involvement of PPAR-γ, NF-κB and Nrf2/HO-1 signaling pathways. PLoS One. 2015;10(7):e0132497. doi:10.1371/journal.pone.0132497 CR - Hao T, Chen C, Yang S, et al. Mangiferin exerts neuroprotective effects against focal cerebral ischemia in mice by regulating NF-κB signaling pathway. Metab Brain Dis. 2023;38(1):383-391. doi:10.1007/s11011-022-01066-6 UR - https://doi.org/10.30934/kusbed.1730683 L1 - https://dergipark.org.tr/tr/download/article-file/5006011 ER -