Ketamine suppresses intestinal TLR4 expression and NF-kappaB activity in lipopolysaccharide-treated rats.
OBJECTIVE
To investigate whether ketamine suppresses lipopolysaccharide (LPS)-induced increase in Toll-like receptor 4 (TLR4) expression and nuclear factor-kappa B (NF-kappaB) activity in the intestines of rats.


METHODS
Six groups of rats received one of the following: normal saline control, LPS (5 mg/kg) plus saline, LPS (5 mg/kg) plus ketamine (0.5 mg/kg), LPS (5 mg/kg) plus ketamine (2.5 mg/kg), LPS (5 mg/kg) plus ketamine (10 mg/kg), or ketamine (10 mg/kg) alone. Intestinal TLR4 mRNA expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and NF-kappaB activity was tested by electrophoretic mobility shift assay (EMSA) 1, 3, or 5 hours after the LPS injection.


RESULTS
Lipopolysaccharide increased TLR4 expression and NF-kappaB activity in the intestines of rats. Ketamine at the dosage of 0.5, 2.5, and 10 mg/kg suppressed the LPS-induced increase in TLR4 expression and NF-kappaB activity. Ketamine alone had no effect.


CONCLUSIONS
The study demonstrated that ketamine inhibits NF-kappaB activation in the intestines of LPS-treated rats, possibly by suppressing TLR4 expression.
Yu
Min
M
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China. minyu001@gmail.com
Shao
Danbing
D
Yang
Jianjun
J
Feng
Shangwu
S
Xu
Jianguo
J
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000187:drug effects
D000700:Analgesics; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D007649:Ketamine