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. 2022 Nov;25(11):1396-1401.
doi: 10.22038/IJBMS.2022.64552.14202.

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

Remon Roshdy Rofaeil  1   2 , Sabreen Mahmoud Ahmed  3 , Haitham Ahmed Bahaa  4 , Ahmad Mahran  4 , Nermeen N Welson  5 , Walaa Yehia Abdelzaher  1
Affiliations

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

Remon Roshdy Rofaeil et al. Iran J Basic Med Sci. 2022 Nov.

Abstract

Objectives: 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.

Keywords: Anti-apoptotic; Anti-inflammatory; Sitagliptin; Toll-like receptor 4; Uterine ischemia.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the timing of the work steps
Figure 2
Figure 2
Effect of sitagliptin on oxidative stress parameters
Figure 3
Figure 3
Effect of sitagliptin on interleukin-6, tumor necrosis factor-α, and Toll-like receptor 4
Figure 4
Figure 4
Photomicrographs of sections in the rat endometrium
Figure 5
Figure 5
Photomicrographs of sections of the rat endometrium
Figure 6
Figure 6
Photomicrographs of the PAS reaction in the rat endometrial sections
Figure 7
Figure 7
Photomicrographs of caspase-3 cytoplasmic immunoreaction in the rat endometrial sections
Figure 8
Figure 8
The histopathologic scores of the uterus
See this image and copyright information in PMC

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