The Role of Oxidative Stress in Decreased Acetylcholinesterase Activity at the Neuromuscular Junction of the Diaphragm during Sepsis.

Hua Liu,Shi-tong Li,Hong Wang,Jun-yan Yao,Jin Wu

doi:10.1155/2017/9718615

Hua Liu, Shi-tong Li + Show 3 more

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https://doi.org/10.1155/2017/9718615

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Abstract

Our recent study demonstrated that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm decreased during sepsis. However, the mechanisms were not clearly identified. In this study, we aimed to investigate whether the decreased AChE activity was related to oxidative stress by observing AChE activity in different grades of sepsis induced by caecal ligation and puncture (CLP). At 24 h after surgery, an assay of thiobarbituric acid reactive species (TBARS) and protein carbonyls, as well as the myeloperoxidase (MPO), superoxide dismutase (SOD), and catalase (CAT) activity, was conducted. AChE activity was measured by biochemical and histological detection. AChE and CAT activity in the diaphragm decreased, while the contents of TBARS and protein carbonyls, the activity of MPO and SOD, and the SOD/CAT ratios increased. The above changes were much more significant in the mid-grade septic group than in the low-grade septic group. The colour of the AChE activity staining at the NMJ gradually lightened from the sham surgery group to the mid-grade septic group. AChE activity was significantly negatively correlated with the levels of TBARS and protein carbonyls. We consider that oxidative stress might be responsible for decreased AChE activity in the diaphragms of rats induced with sepsis.

Highlights

Sepsis is a clinical syndrome caused by severe infection, leading to multiple organ dysfunction [1, 2]
Our recent study has reported that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm was inhibited during sepsis [3]
Using low-grade and midgrade models of sepsis in rats, this study found that the AChE and CAT activities in the diaphragm decreased, while the contents of thiobarbituric acid reactive species (TBARS) and protein carbonyls, the activity of MPO and superoxide dismutase (SOD), and the SOD/CAT ratios increased at 24 h after caecal ligation and puncture (CLP) surgery

Summary

Introduction

Sepsis is a clinical syndrome caused by severe infection, leading to multiple organ dysfunction [1, 2]. Our recent study has reported that acetylcholinesterase (AChE) activity at the neuromuscular junction (NMJ) of the diaphragm was inhibited during sepsis [3]. The effects of different grades of sepsis on the activity of AChE were not illustrated in that study. The mechanisms through which AChE activity was inhibited during sepsis were not clearly identified. Previous studies have demonstrated that several factors, including inflammatory, immune, hormonal, metabolic, and bioenergetic responses, were involved in the pathogenesis of sepsis [4,5,6]. One of the crucial factors in these processes is the loss of balance between the reactive species (ROS)

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