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

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.

Changes in murine anorectum signaling across the life course

“…Previous work on aged GI tract has shown an increase in reactive oxygen species in animal models with increasing age, although similar changes in the humans have not been so clearly documented . Oxidative stress has also been demonstrated to reduce cholinesterase activity in a range of tissues providing a potential mechanism for changes observed in this study …”

“…40 Oxidative stress has also been demonstrated to reduce cholinesterase activity in a range of tissues providing a potential mechanism for changes observed in this study. [41][42][43] About 1 μmol L −1 physostigmine has been shown to completely block cholinesterase activity in other GI tract smooth muscles.…”

Neuregulin-1β Protects the Rat Diaphragm during Sepsis against Oxidative Stress and Inflammation by Activating the PI3K/Akt Pathway

“…Muscle relaxant antagonists exert their therapeutic effect by inhibiting AChE activity, which causes more acetylcholine release and ultimately accelerates muscle function restoration [12]. Our previous study verified that AChE activity decreased at the NMJ in the diaphragm during sepsis and oxidative stress was a vital contributor [13]. Drugs could inhibit the inflammation, and/or oxidative stress is theoretically useful for maintaining diaphragmatic contractile function and AChE activity during sepsis.…”

Differences in Inflammation, Apoptosis and Tissue Hypo-perfusion Indicators Caused by Using Two Different Gauges in Cecal Ligation and Puncture-induced Rat Models of Sepsis

“…(25)(26)(27)(28)(29)(30) It is demonstrated that sepsis induced by both gauge 18 and gauge 21can elevate ROS levels in the liver, colon and kidney 16 to 24 hours following the procedure (31)(32)(33)(34). In addition, 6 to 48 hours after the procedure, LPO level, increases in the lung, ileum, diaphragm, heart, brain and kidney (regardless of the gauges used) (26)(27)(28)(29)(30)(34)(35)(36)(37)(38)(39)(40)(41). Congruently, the ndings of our study demonstrated that 24 hours after the CLP procedure, in both cardiac and pulmonary tissues, oxidative stress markers increased, whereas the levels of antioxidant indicators reduced in comparison with the sham group.…”