Effect of trimetazidine against ovarian ischemia/reperfusion injury in rat model: A new pathway: JAK2/STAT3

Document Type : Original Article

Authors

1 Department of Pharmacology, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, Türki̇ye

2 Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Türki̇ye

3 Clinical Research, Development and Design Application and Research Center, Ataturk University, Erzurum, Türki̇ye

4 Department of Histology and Embryology, Faculty of Medicine, Kafkas University, Kars, Türki̇ye

5 Department of Pharmacology, Faculty of Pharmacy, Van Yuzuncu Yıl University, Van, Türki̇ye

Abstract

Objective(s): Ovarian ischemia/reperfusion (I/R) is an extremely complex pathological problem that begins with oxygen deprivation, progresses to excessive free radical production, and intensifies inflammation. The JAK2/STAT3 signaling pathway is a multipurpose signaling transcript channel that plays a role in several biological functions. Trimetazidine (TMZ) is a cellular anti-ischemic agent. This study aims to investigate the effects of TMZ on ovarian I/R injury in rats.
Materials and Methods: sixty four rats were divided into 8 groups at random: healthy(group1); healthy+TMZ20(group2); ischemia (I) (group 3); I+TMZ10(group4); I+ TMZ20(group5); I/R(group6); I/R+TMZ10(group7); I/R+TMZ20(group8). Vascular clamps were placed just beneath the ovaries and over the uterine horns for 3 hr to induce ischemia. The clamps were removed for the reperfusion groups, and the rats were reperfused with care to ensure that the blood flowed into the ovaries, subjecting them to reperfusion for 3 hr. TMZ was administered orally by gavage 6 and 1 hr before operations. At the end of the experiment, ovarian tissues were removed for biochemical, molecular, and histopathological investigation.
Results: TMZ administration ameliorated ischemia/reperfusion-induced disturbances in GSH and MDA levels. TMZ treatment inhibited I/R-induced JAK2/STAT3 signaling pathway activation in ovarian tissues. TMZ administration also improved the increase in the mRNA expressions of IL-1β, TNF-α, and NF-κB caused by ischemia/reperfusion injury. Moreover, TMZ treatment improved histopathologic injury in ovarian tissues caused by ischemia/reperfusion.
Conclusion: TMZ treatment protected rats against ovarian ischemia/reperfusion injury by alleviating oxidative stress and inflammatory cascades. These findings may provide a mechanistic basis for using TMZ to treat ovarian ischemia-reperfusion injury.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 11
November 2023
Pages 1370-1379

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