Resveratrol Inhibits the Inflammatory Response and Oxidative Stress Induced by Uterine Ischemia Reperfusion Injury by Activating PI3K-AKT Pathway

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Jun 24

PMID 35749345

Authors

Ying Wang

Yong Wu

Shu Peng

Affiliations

Soon will be listed here.

Abstract

Uterus transplantation is a complex surgical procedure. Uterine ischemia reperfusion (I/R) injury that occurs during this process may cause a loss of function of the uterus and the failure of transplantation. Resveratrol (RSV) is a naturally occurring polyphenol found abundantly in the skin of grapes and red wine, and it has also been used as a dietary supplement in clinical practice. RSV possesses strong anti-inflammatory and anti-oxidative effects, and exhibits a role in immune system regulation. However, the role of RSV in protecting the uterus against I/R-induced injury is yet to be fully elucidated. The aim of the present study was to investigate the effects and mechanisms underlying RSV in I/R-induced uterus injury. A total of 48 Sprague-Dawley rats were randomly divided into four groups: Control (sham operation) group, the uterus I/R group, the 20 mg/kg RSV-pre-treated I/R (I/R+RSV/20) group and the 40 mg/kg RSV-pre-treated I/R (I/R+ RSV/40) group. A regular I/R model was established to induce uterus injury in rats. RSV at 20 or 40 mg/kg was intraperitoneally administrated into rats in both I/R+ RSV groups once per day for five consecutive days prior to ischemia. The control and I/R only groups received an intraperitoneal injection of the vehicle (ethanol) for the same period prior to ischemia. Samples from blood and uterine horns were collected 3 h after reperfusion. Changes in the levels of malondialdehyde, interleukin (IL)-6, tumor necrosis factor-α, IL-10 and IL-37 were determined using ELISA, the activity levels of myeloperoxidase, catalase, and superoxidase dismutase were also determined using ELISA, the protein expression levels of PI3K, phosphorylated (p)-PI3K, AKT and p-AKT were determined using western blot analysis, and the uterine histology was investigated using H&E staining. Results of the present study demonstrated that treatment with RSV increased the capacity of antioxidants and suppressed uterine oxidative injury induced by I/R. Moreover, treatment with RSV decreased the levels of pro-inflammatory cytokines and increased the levels of anti-inflammatory cytokines. In addition, RSV promoted the phosphorylation of PI3K and AKT, thus activating the PI3K-AKT signaling pathway. Therefore, administration of RSV prior to uterine I/R effectively alleviated inflammatory response and oxidative stress via activation of the PI3K-AKT pathway, suggesting that RSV may play a protective role in I/R-induced uterus injury.

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