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.
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.
Ochiai
Jun
J
First Department of Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Takano
Hirohisa
H
Ichikawa
Hiroshi
H
Naito
Yuji
Y
Yoshida
Norimasa
N
Yanagisawa
Rie
R
Yoshino
Shin
S
Murase
Hironobu
H
Yoshikawa
Toshikazu
T
D000208:Acute Disease; D000818:Animals; D002839:Chromans / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000401:mortality*; D005786:Gene Expression Regulation / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011654:Pulmonary Edema / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
C106323:2-(glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol; D002839:Chromans; D016207:Cytokines; D006027:Glycosides; D008070:Lipopolysaccharides; D014810:Vitamin E