Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats

Objective(s): Uterine ischemia is a common problem with ongoing controversy about its pathogenesis and prevention. The present study aimed to investigate the protective role of sitagliptin against uterine ischemia-reperfusion injury (IRI). Materials and Methods: Rats were allocated into 4 groups: co...

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Main Authors: Remon Rofaeil, Sabreen Ahmed, Haitham Bahaa, Ahmad Mahran, Nermeen Welson, Walaa Abdelzaher
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2022-11-01
Series:Iranian Journal of Basic Medical Sciences
Subjects:
Online Access:https://ijbms.mums.ac.ir/article_21108_e57ff6f9d2fb1481522198206c9f666e.pdf
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author Remon Rofaeil
Sabreen Ahmed
Haitham Bahaa
Ahmad Mahran
Nermeen Welson
Walaa Abdelzaher
author_facet Remon Rofaeil
Sabreen Ahmed
Haitham Bahaa
Ahmad Mahran
Nermeen Welson
Walaa Abdelzaher
author_sort Remon Rofaeil
collection DOAJ
description Objective(s): Uterine ischemia is a common problem with ongoing controversy about its pathogenesis and prevention. The present study aimed to investigate the protective role of sitagliptin against uterine ischemia-reperfusion injury (IRI). Materials and Methods: Rats were allocated into 4 groups: control, sitagliptin (SIT) (5 mg/kg), IR; ischemia was induced followed by reperfusion, and IR+SIT; SIT was administered 1 hr before IRI. Uteri were removed for histopathological and biochemical observations. Malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), superoxide dismutase (SOD) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and toll-like receptor 4 (TLR4) were all measured. Hematoxylin and eosin (H&E) stain, Periodic acid-Schiff stain (PAS), and caspase-3 immunostaining were applied. Results: In the IR+SIT group; NOx, GSH, and SOD activities increased significantly. Meanwhile, the levels of MDA, TNF-α, IL-6, TLR4, and caspase-3 immunoexpression showed a significant reduction, as compared with the IR group. In the IR+SIT group, an improvement in the histopathological picture was noticed.Conclusion: The results showed that sitagliptin confers protection against uterine IRI through anti-oxidant, anti-inflammatory, and anti-apoptotic effects with a possible role for TLR4.
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spelling doaj.art-7f6a40b0c4f44dafad9b785859bdaf2b2022-12-22T03:56:24ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-11-0125111396140110.22038/ijbms.2022.64552.1420221108Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in ratsRemon Rofaeil0Sabreen Ahmed1Haitham Bahaa2Ahmad Mahran3Nermeen Welson4Walaa Abdelzaher5Department of Pharmacology, Faculty of Medicine, Minia University, Minia, EgyptDepatment of Human Anatomy and Embryology, Faculty of Medicine, Minia University, delegated to Deraya University-New Minia City, EgyptDepartment of Obstetrics and Gynecology, Faculty of Medicine, Minia University. Minia, EgyptDepartment of Obstetrics and Gynecology, Faculty of Medicine, Minia University. Minia, EgyptDepartment of Forensic medicine and clinical toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef, EgyptDepartment of Pharmacology, Faculty of Medicine, Minia University, Minia, EgyptObjective(s): Uterine ischemia is a common problem with ongoing controversy about its pathogenesis and prevention. The present study aimed to investigate the protective role of sitagliptin against uterine ischemia-reperfusion injury (IRI). Materials and Methods: Rats were allocated into 4 groups: control, sitagliptin (SIT) (5 mg/kg), IR; ischemia was induced followed by reperfusion, and IR+SIT; SIT was administered 1 hr before IRI. Uteri were removed for histopathological and biochemical observations. Malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), superoxide dismutase (SOD) activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and toll-like receptor 4 (TLR4) were all measured. Hematoxylin and eosin (H&E) stain, Periodic acid-Schiff stain (PAS), and caspase-3 immunostaining were applied. Results: In the IR+SIT group; NOx, GSH, and SOD activities increased significantly. Meanwhile, the levels of MDA, TNF-α, IL-6, TLR4, and caspase-3 immunoexpression showed a significant reduction, as compared with the IR group. In the IR+SIT group, an improvement in the histopathological picture was noticed.Conclusion: The results showed that sitagliptin confers protection against uterine IRI through anti-oxidant, anti-inflammatory, and anti-apoptotic effects with a possible role for TLR4.https://ijbms.mums.ac.ir/article_21108_e57ff6f9d2fb1481522198206c9f666e.pdfanti-apoptoticanti-inflammatorysitagliptintoll-like receptor 4uterine ischemia
spellingShingle Remon Rofaeil
Sabreen Ahmed
Haitham Bahaa
Ahmad Mahran
Nermeen Welson
Walaa Abdelzaher
Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
Iranian Journal of Basic Medical Sciences
anti-apoptotic
anti-inflammatory
sitagliptin
toll-like receptor 4
uterine ischemia
title Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
title_full Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
title_fullStr Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
title_full_unstemmed Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
title_short Dipeptidyl peptidase-4 inhibitor: Sitagliptin down-regulated toll-like receptor 4 signaling pathway to reduce uterine injury in rats
title_sort dipeptidyl peptidase 4 inhibitor sitagliptin down regulated toll like receptor 4 signaling pathway to reduce uterine injury in rats
topic anti-apoptotic
anti-inflammatory
sitagliptin
toll-like receptor 4
uterine ischemia
url https://ijbms.mums.ac.ir/article_21108_e57ff6f9d2fb1481522198206c9f666e.pdf
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