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.

Downregulation of miR‐497‐5p prevents liver ischemia‐reperfusion injury in association with MED1/TIMP‐2 axis and the NF‐κB pathway

“…The liver I/R injury process causes the aggregation and activation of downstream adaptor proteins and signal kinases. 23 The evidence derived from our study suggested that miR-497-5p, MED1/TIMP2 and the NF-κB signaling pathway affect the inflammatory responses in liver I/R injury. Initially, our study suggested that miR-497-5p was highly expressed in liver I/R injury both in vivo and in vitro.…”

Vagus Nerve Stimulation Attenuates Acute Skeletal Muscle Injury Induced by Hepatic Ischemia/Reperfusion Injury in Rats

“…Cui et al ( Cui et al, 2018 ) found that the protection of short-acting opioids against I/R injury in multiple organs, including the liver, acts through the central vagus pathway. Many studies have reported that VNS can alleviate hepatic I/R injury and skeletal muscle I/R injury by inhibiting inflammation and alleviating oxidative stress ( Zhang et al, 2019a ; Zhang et al, 2019b ; Lai et al, 2019 ; Xia et al, 2020 ). Medeiros et al ( Lauz Medeiros et al, 2016 ) found that antioxidants protect against intestinal damage caused by hepatic I/R injury by reducing inflammation and oxidative stress.…”

Hepatic ischemia reperfusion injury: effect of moderate intensity exercise and oxytocin compared to l-arginine in a rat model

“…Hepatic IR resulted in hepatic injury as proved by increased level of liver enzymes. Hepatic IR causes the disruption of the membrane stability of hepatocytes due to necrosis, cellular damage, and structural changes with release of large quantities of liver enzymes [37][38][39].…”