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A NOVEL WATER‐SOLUBLE VITAMIN E DERIVATIVE PREVENTS ACUTE LUNG INJURY BY BACTERIAL ENDOTOXIN
Author(s) -
Uchiyama Kazuhiko,
Takano Hirohisa,
Yanagisawa Rie,
Inoue Kenichiro,
Naito Yuji,
Yoshida Norimasa,
Yoshino Shin,
Murase Hironobu,
Ichinose Takamichi,
Yoshikawa Toshikazu
Publication year - 2004
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2004.03981.x
Subject(s) - chemokine , lipopolysaccharide , bronchoalveolar lavage , chemistry , pharmacology , lung , macrophage inflammatory protein , infiltration (hvac) , inflammation , chemotaxis , immunology , medicine , biochemistry , physics , receptor , thermodynamics
SUMMARY 1. Various chemokines, such as keratinocyte chemoattractant (KC), macrophage inflammatory protein (MIP)‐1α 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‐(α‐ 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 µg/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‐1α 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.