Can monomethyl fumarate and nifedipine reduce ischemia reperfusion injury in rat ovary, and what is the share of oxidative stress-sensitive transcription factors HIF-1a, Nfkb, and Nrf2?

Document Type : Original Article

Authors

1 Sivas Cumhuriyet University, Faculty of Medicine, Department of Obstetrics and Gynecology, Sivas, Turkey

2 Sivas Cumhuriyet University, Faculty of Medicine, Department of Histology & Embryology, Sivas, Turkey

3 Sivas Cumhuriyet University, Faculty of Science, Department of Biology, Sivas, Turkey

4 Acibadem Mehmet Ali Aydinlar University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Istanbul, Turkey

5 Health Sciences University, Haseki Training and Research Hospital, Department of Obstetrics and Gynecology, Istanbul, Turkey

10.22038/ijbms.2026.89192.19254

Abstract

Objective(s): This study aimed to investigate the potential protective roles of monomethyl fumarate (MMF) and nifedipine (NF) against ovarian ischemia-reperfusion (I/R) injury in rats, with a particular focus on the contribution of oxidative stress-sensitive transcription factors HIF-1α, NF-κB, and Nrf2.
Materials and Methods: A rat model of ovarian I/R injury was established using 3-hr ischemia followed by 24-hour reperfusion. Ovarian hormone secretion capacity, oxidative stress-related biomolecular alterations, and apoptosis activation were analyzed using ELISA. Histopathological damage and apoptotic cell status were evaluated by hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining. Expression levels of HIF-1α, NF-κB, Nrf2, and related downstream genes were determined using RT-qPCR.
Results: I/R significantly altered the expression of oxidative stress-associated transcription factors and their downstream targets compared with ischemia alone (P<0.05). Combined administration of MMF and NF restored serum AMH and E2 levels toward control values and reduced tissue oxidative stress markers (TOS and MDA). Gene expression of pro-apoptotic (BAX, BECLIN-1) and stress-related (HIF-1α, NF-κB, Nrf2) molecules improved under MMF and NF treatments. The combined therapy showed the most effective reduction in oxidative stress-induced molecular and histological alterations.
Conclusion: MMF and NF exerted protective effects against ovarian I/R injury by modulating oxidative stress and apoptosis. These findings suggest that the coordinated regulation of HIF-1α, NF-κB, and Nrf2 pathways may play a pivotal role in reducing reperfusion-related ovarian tissue damage.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 29, Issue 3
March 2026
Pages 446-457

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