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

Document Type : Original Article


1 Department of Pharmacology, Faculty of Medicine, Minia University, Minia, Egypt

2 Department of Pharmacology, Faculty of Pharmacy, Deraya University, Minia, Egypt

3 Depatment of Human Anatomy and Embryology, Faculty of Medicine, Minia University, delegated to Deraya University-New Minia City, Egypt

4 Department of Obstetrics and Gynecology, Faculty of Medicine, Minia University. Minia, Egypt

5 Department of Forensic medicine and clinical toxicology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt


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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