Sevoflurane protects the liver from ischemia-reperfusion injury by regulating Nrf2/HO-1 pathway.

Abstract

We aimed to investigate the role and mechanism of sevoflurane (SEV) preconditioning in liver ischemia-reperfusion (I/R) injury. In vivo, rats were randomly divided into Sham group, I/R rat model group, I/R + SEV group and SEV group. In vitro, hypoxia-reoxygenation (H/R) cell model were established. Hematoxylin-Eosin (H&E) and TUNEL assay were used to evaluate the degree of tissue damage and detect apoptosis in rats, respectively. HO-1, nuclear Nrf2 and cytosolic Nrf2 expressions were detected by immunohistochemical staining, Western blot analysis and quantitative real-time PCR (qRT-PCR), respectively. Contents of Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) were determined by corresponding kits. Inflammatory factor levels, cell viability, apoptosis were detected by enzyme-linked immunosorbent assay (ELISA), MTT assay, and flow cytometry, respectively.In the I/R group, liver damage was severe, apoptosis-positive cells were increased, HO-1 and nuclear Nrf2 expressions were increased, and cytosolic Nrf2 expression was decreased. After SEV pretreatment, the degree of liver injury and apoptosis in rats were significantly reduced, HO-1 and nuclear Nrf2 expressions were increased significantly, and cytosolic Nrf2 expression was decreased. 4% SEV had the best mitigating effect on H/R-induced liver cell damage, as evidenced by reduced contents of LDH and MDA, decreased inflammatory factors, a lowered apoptosis rate, inhibited ROS production, effectively promoted Nrf2 nucleation, and activated Nrf/HO-1 pathway. ML385 pretreatment significantly inhibited the effect of SEV on hepatocytes.Sevoflurane protects the liver from ischemia-reperfusion injury by regulating the Nrf2/HO-1 pathway.

• Authors: Hongyan Ma, Baoyi Yang, Lu Yu, Yang Gao, Xiangmei Ye, Ying Liu, Zhengtian Li, Hulun Li, Enyou Li
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 898 Pg. 173932 (May 05 2021) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 33631180 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Inflammation Mediators
• Membrane Proteins
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Reactive Oxygen Species
• Sevoflurane
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Hmox1 protein, rat

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line
• Disease Models, Animal
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Heme Oxygenase-1 (genetics, metabolism)
• Hepatocytes (drug effects, enzymology, pathology)
• Inflammation Mediators (metabolism)
• Liver (drug effects, enzymology, pathology)
• Liver Diseases (enzymology, pathology, prevention & control)
• Male
• Membrane Proteins (genetics, metabolism)
• Mice
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (enzymology, pathology, prevention & control)
• Sevoflurane (pharmacology)
• Signal Transduction
• Rats