Protective effects of Nrf2 against sepsis-induced hepatic injury.

Abstract

AIM:

This study was designed to investigate the changes of liver injury and Nrf2 signaling pathway in the process of sepsis. We also aimed to examine the role of Nrf2 in resisting oxidative stress and relieving inflammation in sepsis-induced hepatic injury.

MAIN METHODS:

By operating cecal ligation and puncture (CLP) on Nrf2-/- mice and wild type mice, a sepsis-induced hepatic injury model was established. We compared and contrasted the wild type mice with the Nrf2-/- mice during sepsis-induced hepatic injury, and evaluated the liver damage by biochemical analyses and staining hematoxylin-eosin (HE). Western blot or real-time PCR was performed to detect Nrf2 and its regulated genes NQO-1, GCLM and HO-1. Additionally, we detected the expressions and secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), IL-1β and anti-inflammatory cytokines IL-10. We assessed the oxidative stress through the levels of MDA and NO.

KEY FINDINGS:

The results showed that Nrf2 expressions at mRNA and protein levels were increased 1 day after CLP, namely the early stage of sepsis. Compared with wild type mice after CLP, Nrf2-/- mice showed more severe liver injury, accompanied by higher expression of inflammatory cytokines and oxidative stress. Notably, Nrf2-regulated genes GCLM and NQO-1, were strongly downregulated in Nrf2-/- mice.

SIGNIFICANCE:

Nrf2 was probably implicated in decreasing inflammatory cytokine levels and counteracting oxidative stress to alleviate sepsis-induced hepatic injury, mainly through regulating GCLM and NQO-1 in the early stage after CLP.

• Authors: Liping Li, Qianwen Zhang, Xi Zhang, Xiaoting Xu, Xinzhi Wang, Xin Huang, Tao Wang, Zhenzhou Jiang, Li Xiao, Luyong Zhang, Lixin Sun
• Journal: Life sciences (Life Sci) Vol. 282 Pg. 119807 (Oct 01 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 34245771 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse

Topics

• Animals
• Gene Expression Regulation
• Liver (injuries, metabolism)
• Liver Diseases (etiology, genetics, metabolism, prevention & control)
• Mice
• Mice, Knockout
• NF-E2-Related Factor 2 (biosynthesis, genetics)
• Oxidative Stress
• Sepsis (complications, genetics, metabolism)