Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation.

Abstract

Inflammation and oxidative stress are pivotal mechanisms for the pathogenesis of ischemia and reperfusion injury (IRI). Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the in vivo VNS can protect the liver from IRI. In this study, hepatic IRI were induced by ligating the vessels supplying the left and middle lobes of the liver, which underwent 1 h occlusion followed with 24 h reperfusion. VNS was initiated 15 min after ischemia and continued 30 min. Hepatic function, histology, and apoptosis rates were evaluated after 24 h reperfusion. Compared with the IRI group, VNS significantly improved hepatic function. The protective effect was accompanied by a reduction in histological damage in the ischemic area, and the apoptosis rate of hepatocytes has considerable reduction. To find the underlying mechanism, proteomic analysis was performed and differential expression of glutathione synthetase (GSS) and glutathione S-transferase (GST) was observed. Subsequently, test results indicated that VNS upregulated the expression of mRNA and protein of GSS and GST. Meanwhile, VNS increased the plasma levels of glutathione and glutathione peroxidases. We found that VNS alleviated hepatic IRI by upregulating the antioxidant glutathione via the GSS/glutathione/GST signaling pathway.

• Authors: Haoyang Xia, Zhongzhong Liu, Wenjin Liang, Xianpeng Zeng, Yi Yang, Pu Chen, Zibiao Zhong, Qifa Ye
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2020 Pg. 1079129 ( 2020) ISSN: 1942-0994 [Electronic] United States
• PMID: 32064020 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Haoyang Xia et al.

Chemical References

• Antioxidants
• Cytokines
• Glutathione Peroxidase
• Glutathione Transferase
• Glutathione Synthase
• Glutathione

Topics

• Animals
• Antioxidants (metabolism)
• Apoptosis (genetics)
• Cytokines (metabolism)
• Glutathione (biosynthesis, blood, metabolism)
• Glutathione Peroxidase (blood)
• Glutathione Synthase (genetics, metabolism)
• Glutathione Transferase (genetics, metabolism)
• Hepatocytes (enzymology, metabolism)
• Liver (enzymology, injuries, metabolism, pathology)
• Liver Diseases (enzymology, metabolism, pathology, therapy)
• Male
• Oxidative Stress
• Proteomics
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (enzymology, metabolism, pathology, therapy)
• Signal Transduction (genetics)
• Vagus Nerve Stimulation