Iranian Journal of Basic Medical Sciences

Iranian Journal of Basic Medical Sciences

Efficacy of finerenone and/or roflumilast in alleviation of intestinal ischemic reperfusion injury via regulation of IL10/AMPK/VEGF/eNOS pathway in rats

Articles in Press

Document Type : Original Article

Authors
Marwa Monier Mahmoud Refaie 1
Randa Ahmed Ibrahim 2, 3
Sayed Shehata 4
Asmaa Ali Muhammed 5, 6
Shereen Mohammed Mohammed Elsaghir 7
Asmaa Salah Mohammed Abd Elfattah 7
Asmaa Alsayed Hasan 8
Amany Haroun AbdelNaiem 9, 3
Nagwa Zenhom Mustafa Ahmed 9, 10
Mohamed Rabie Saad 11
Doaa Mohamed Elroby Ali 12
Heba Adel Habib 13
Nardien Ekram Haliem Saleh 14
1 Department of Medical Pharmacology, Faculty of Medicine, Minia University, 61511, Minia, Egypt Faculty of Medicine, Minia National University, Minia, Egypt.
2 Department of Histology and Cell Biology, Faculty of Medicine, Minia University, 61511, Minia, Egypt
3 Faculty of Medicine, Minia National University, Minia, Egypt
4 Department of Cardiology, Faculty of Medicine, Minia University, 61511, Minia, Egypt
5 Department of Medical Physiology, Faculty of Medicine, Aswan University, 81528, Aswan, Egypt
6 Department of Physiology, RAK College of Medical Sciences, RAK Medical & Health Sciences University, Ras-AlKhaimah 11127, United Arab Emirates
7 Department of Internal Medicine, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt
8 Department of Human Anatomy and Embryology, Faculty of Medicine, Aswan University, 81528, Aswan, Egypt
9 Department of Medical Biochemistry, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt
10 Department of Biochemistry, Faculty of Medicine, Al-Baha University, Albaha 65525, Saudi Arabia
11 Department of Surgery, Faculty of Medicine, Aswan University, 81528, Aswan, Egypt
12 Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Sohag University, 82524, Sohag, Egypt
13 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, 61511, El-Minia, Egypt
14 Department of Medical Physiology, Faculty of Medicine, Minia University, 61511, El-Minia, Egypt
10.22038/ijbms.2026.94574.20397
Abstract
Objective(s): Intestinal ischemia is a serious emergency that requires immediate management and surgical intervention. Finding an effective therapeutic strategy, in addition to surgical treatment, is essential to mitigate the harmful effects of intestinal ischemia-reperfusion (IIR)-induced tissue injury not only in the intestine itself but also in distant organs, especially the liver. This prompted us to evaluate, for the first time, the role of finerenone (FIN), a non-steroidal selective mineralocorticoid receptor antagonist, and/or roflumilast (ROF), a selective phosphodiesterase 4 inhibitor, in experimentally induced IIR injury in both hepatic and intestinal tissues, with a detailed study of various mechanisms.
Materials and Methods: Wistar rats were randomly assigned to 5 groups (N=10): Sham group, IIR group, FIN/ROF, FIN, and ROF-administered groups, with IIR induction.
Results: Interestingly, FIN/ROF significantly reduced elevated levels of liver function enzymes, tissue malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), caspase-3 expression, and aldosterone. Furthermore, FIN/ROF could normalize the tissue level of interleukin 10 (IL-10), adenosine monophosphate‐activated protein kinase (AMPK), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), antioxidant parameters, reduced glutathione (GSH), and total antioxidant capacity (TAC) with remarkable improvement in the histopathological features.
Conclusion: FIN/ROF could mitigate IIR-induced hepatic and intestinal damage via FIN-mediated blockade of mineralocorticoid receptors and ROF-mediated inhibition of phosphodiesterase 4, and through antioxidant, anti-apoptotic, and anti-inflammatory properties with regulation of the IL-10/AMPK/VEGF/eNOS pathway. Thus, FIN/ROF is a potential medical treatment for IIR, in addition to surgery.
Keywords
Endothelial nitric oxide- synthase
Finerenone
Intestinal ischemia-reperfusion
Roflumilast
Vascular endothelial growth-factor
Subjects
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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 05 August 2026