Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis factor alpha in rats with lipopolysaccharide-induced peritonitis.
BACKGROUND
The nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine.


METHODS
Rat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group.


RESULTS
The level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy.


CONCLUSIONS
Cholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.
Liu
Zhi-Hai
ZH
Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine and Research Institute of Emergency Medicine, Hangzhou, Zhejiang 310009, China.
Ma
Yue-Feng
YF
Wu
Jun-Song
JS
Gan
Jian-Xin
JX
Xu
Shao-Wen
SW
Jiang
Guan-Yu
GY
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D005702:Galantamine / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D002800:Cholinesterase Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005702:Galantamine