The liver protection of propylene glycol alginate sodium sulfate preconditioning against ischemia reperfusion injury: focusing MAPK pathway activity

Shizan Xu,Xiaoming Fan,Wenhui Mo,Yujing Xia,Wenwen Wang,Peiqin Niu,Liwei Wu,Xiya Lu,Tong Liu,Kan Chen,Fan Wang,Ling Xu,Ning Liu,Qiang Yu,Jingjing Li,Jiao Feng,Weiqi Dai,Sainan Li,Chuanyong Guo

doi:10.1038/s41598-017-15521-3

Abstract

Hepatic ischemia reperfusion (IR) injury contributes to the morbidity and mortality associated with liver surgery. This study investigated the protective function and mechanism of propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide, in a mouse hepatic IR injury model. PSS (25 or 50 mg/kg) or saline were injected intraperitoneally to male Balb/c mice 1 h before 45 min of 70% warm hepatic ischemia and 2, 8, and 24 h of reperfusion. Serum and liver tissue samples were collected for evaluation of hepatocellular damage, liver histology, and assay of inflammatory cytokines, apoptosis- and autophagy-related proteins, and proteins in the mitogen-activated protein kinase (MAPKs). Histological injury and release of transaminases, and inflammatory cytokine production were significantly reduced by PSS pretreatment. The expression of apoptosis- and autophagy-related proteins, and the activation of MAPK signal, including jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and P38 were all affected by PSS treatment compared with IR model controls. PSS protected the liver from IR injury by suppressing the MAPK signaling and down-regulating inflammation, apoptosis, and autophagy.

Highlights

Hepatic ischemia reperfusion (IR) injury, a reaction to the sudden re-establishment of blood supply following a period of hypoxia, is a clinical consequence of liver transplantation, hepatic resection, severe trauma, and hemorrhagic shock[1,2]
In apoptosis, programmed cell death is initiated by either extrinsic or intrinsic pathways that activate caspases such as caspase 3 and 916–18. Autophagy is another form of programmed cell death that occurs with hepatic IR injury
The toxicity of propylene glycol alginate sodium sulfate (PSS) was evaluated by changes in liver enzymes, expression of some inflammation, apoptosis, and autophagy proteins, and pathological examination

Summary

Introduction

Hepatic ischemia reperfusion (IR) injury, a reaction to the sudden re-establishment of blood supply following a period of hypoxia, is a clinical consequence of liver transplantation, hepatic resection, severe trauma, and hemorrhagic shock[1,2]. Cellular signaling that is activated in hepatic IR injury includes members of the mitogen-activated protein kinase (MAPKs) family[2,7,14], and inhibition of the MAPKs pathway is known to be protective. Both apoptosis and necrosis occur in vivo with hepatic IR injury[15]. In apoptosis, programmed cell death is initiated by either extrinsic or intrinsic pathways that activate caspases such as caspase 3 and 916–18 Autophagy is another form of programmed cell death that occurs with hepatic IR injury.

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Conclusion