Over İskemi-Reperfüzyon Hasarı ve Mangiferin’in Olası Rolü: Histopatolojik ve Biyokimyasal Bir İnceleme

Abstract

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.

Keywords

• Anti Müllerian Hormon
• Histopatoloji
• İskemi Reperfüzyon Hasarı
• Mangiferin
• Over

Project Number

BAP Project no: TIP.24.028

Ovarian Ischemia-Reperfusion Injury and the Potential Role of Mangiferin: A Histopathological, Biochemical Investigation

Abstract

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.

Keywords

• Anti Müllerian Hormone
• Histopathology
• İschemia Reperfusion İnjury
• Mangiferin
• Ovary

Supporting Institution

Dicle University Scientific Research Platform (DUBAP) (BAP Project no: TIP.24.028)

Project Number

BAP Project no: TIP.24.028

Ethical Statement

Ethical approval for this study was obtained from the Dicle University Animal Experiments Local Ethics Committee (Approval Date: June 21, 2023; Approval No: 6). All procedures were conducted in accordance with institutional ethical guidelines

Thanks

The authors would like to thank the Scientific Research Platform of Dicle University (DUBAP) for their financial support. They also express their sincere gratitude to their colleague Özlem Demir for her valuable contributions to this study.

References

1. 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/
2. 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
3. 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
4. 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
5. 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
6. 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
7. 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
8. 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

9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. 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
23. 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
24. 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
25. 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
26. 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
27. 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