Dipeptidyl peptidase-۴ inhibitor: Sitagliptin down-regulated toll-like receptor ۴ 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 ۴ groups: control, sitagliptin (SIT) (۵ mg/kg), IR; ischemia was induced followed by reperfusion, and IR+SIT; SIT was administered ۱ 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-۶ (IL-۶), and toll-like receptor ۴ (TLR۴) were all measured. Hematoxylin and eosin (H&E) stain, Periodic acid-Schiff stain (PAS), and caspase-۳ immunostaining were applied. Results: In the IR+SIT group; NOx, GSH, and SOD activities increased significantly. Meanwhile, the levels of MDA, TNF-α, IL-۶, TLR۴, and caspase-۳ 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 TLR۴.

Keywords:

Anti-apoptotic , Anti-inflammatory , Sitagliptin , Toll-like receptor ۴ , Uterine ischemia