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A novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, protects against acute lung injury and mortality in endotoxemic rats.

Abstract
Satisfactory therapy for acute lung injury related to endotoxemia remains to be established. However, in vivo antioxidant treatment with N-acetylcysteine reportedly suppresses acute lung injury and proinflammatory cytokine production induced by endotoxin (lipopolysaccharide, LPS). In addition, intrinsic vitamin E is protective against LPS-induced insults. We determined the effects of a novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on acute lung injury and mortality induced by LPS in rats. Intravenous injection of TMG (4 or 40 mg/kg) effectively decreased mortality and prevented the increased alveolar permeability and pulmonary edema that were caused by intravenous injection of LPS (20 mg/kg). Treatment with TMG decreased the enhanced lung expression of TNF-alpha caused by LPS. TMG also suppressed the sequestration of neutrophils in the lung induced by LPS. These results indicate that TMG is a possible therapeutic agent for acute lung injury and mortality, especially that caused by gram-negative bacteria. The therapeutic effects could be mediated at least partly through suppression of the increased expression of TNF-alpha and neutrophil sequestration in the lung that are caused by LPS.
AuthorsJun Ochiai, Hirohisa Takano, Hiroshi Ichikawa, Yuji Naito, Norimasa Yoshida, Rie Yanagisawa, Shin Yoshino, Hironobu Murase, Toshikazu Yoshikawa
JournalShock (Augusta, Ga.) (Shock) Vol. 18 Issue 6 Pg. 580-4 (Dec 2002) ISSN: 1073-2322 [Print] United States
PMID12462569 (Publication Type: Journal Article)
Chemical References
  • 2-(glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol
  • Chromans
  • Cytokines
  • Glycosides
  • Lipopolysaccharides
  • Vitamin E
Topics
  • Acute Disease
  • Animals
  • Chromans (pharmacology)
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Endotoxemia (complications, mortality)
  • Gene Expression Regulation (drug effects)
  • Glycosides (pharmacology)
  • Lipopolysaccharides (antagonists & inhibitors, pharmacology)
  • Lung (blood supply, drug effects, immunology, pathology)
  • Molecular Structure
  • Neutrophils (drug effects, immunology)
  • Pulmonary Edema (pathology, prevention & control)
  • Rats
  • Rats, Wistar
  • Solubility
  • Vitamin E (analogs & derivatives, pharmacology)

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