MitoQ Modulates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction via Regulating Nrf2 Signaling.

Abstract:

Background:Gut barrier dysfunction with alterant mucosal permeability during sepsis is a challenge problem in clinical practice. Intestinal epithelial cells (IECs) are strongly involved in mucosal oxidative stress and inflammatory response. The current study aimed at investigating the effect of MitoQ, a mitochondrial targeted antioxidant, in the treatment of intestinal injury and its potential mechanism during sepsis. Methods:30 minutes before sepsis induction by lipopolysaccharide (LPS) treatment, mice were treated with MitoQ. Intestinal histopathology, mucosal permeability, inflammatory cytokines, and mucosal barrier proteins were evaluated in the present study. Results:MitoQ pretreatment significantly decreased the levels of plasma diamine oxidase, D-lactate, and intestinal histological damage and markedly restored the levels of tight junction proteins (ZO-1 and occludin) following LPS challenge. Furthermore, MitoQ inhibited the LPS-induced intestinal oxidative stress and inflammatory response, evidenced by increased levels of intestinal superoxide dismutase and glutathione, and decreased levels of intestinal IL-1, IL-6, TNF-α, and nitric oxide levels. Mechanically, we found that MitoQ inhibited the oxidative stress via activating nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream antioxidant genes, including HO-1, NQO-1, and GCLM. Conclusions:MitoQ exerts antioxidative and anti-inflammatory effects against sepsis-associated gut barrier injury by promoting Nrf2 signaling pathway.

journal_name

Mediators Inflamm

authors

Zhang S,Zhou Q,Li Y,Zhang Y,Wu Y

doi

10.1155/2020/3276148

subject

Has Abstract

pub_date

2020-04-11 00:00:00

pages

3276148

eissn

0962-9351

issn

1466-1861

journal_volume

2020

pub_type

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