A novel water-soluble vitamin E derivative prevents acute lung injury by bacterial endotoxin.
1. Various chemokines, such as keratinocyte chemoattractant (KC), macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1, are involved in the pathogenesis of acute lung injury induced by bacterial endotoxin (lipopolysaccharide; LPS). Oxidative stress is an important regulator of the expression of these chemokines, whereas vitamin E protects against LPS-induced insults. In the present study, we determined the effects of 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), a novel water-soluble vitamin E derivative with excellent anti-oxidant activity, on acute lung injury induced by intratracheal instillation of LPS (125 micro g/kg) in mice. 2. When TMG was administered intratracheally and intravenously (0.1, 1.0 or 10 mg/kg), it dose-dependently decreased the infiltration of neutrophils into bronchoalveolar lavage fluid after LPS challenge. 3. Histological examination showed that treatment with TMG ameliorated the LPS-induced infiltration of neutrophils into the lungs. Furthermore, TMG attenuated the LPS-induced increase in pulmonary expression of KC, MIP-1alpha and MCP-1 at both the transcriptional and translational levels. 4. These results indicate that TMG is a possible treatment for acute lung injury, especially that caused by Gram-negative bacteria. The therapeutic effect of TMG may be mediated, at least in part, by suppression of the local expression of chemokines, possibly through its strong anti-oxidant activity.
Uchiyama
Kazuhiko
K
First Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Inoue
Ken-ichiro
K
Naito
Yuji
Y
Yoshida
Norimasa
N
Yoshino
Shin
S
Murase
Hironobu
H
Ichinose
Takamichi
T
Yoshikawa
Toshikazu
T
D000818:Animals; D018925:Chemokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014867:Water / Q000378:metabolism
D018925:Chemokines; D008070:Lipopolysaccharides; D014867:Water; D014810:Vitamin E