A novel water-soluble vitamin E derivative protects against aspirin-induced gastric mucosal injury in rats.
Oxygen radical-mediated lipid peroxidation and neutrophil activation may be involved in the development of gastric mucosal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs). Vitamin E is one of the lipid-soluble antioxidants and is generally considered to protect against lipid peroxidation of the cell membrane and to scavenge singlet oxygen and superoxide anion radicals. Our object was to investigate the antioxidative effects of water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetra-methylchroman-6-ol (TMG), on aspirin-induced gastric mucosal injury in rats. Gastric injury was induced by intragastric administration of aspirin and 0.15 N HCl in male Sprague-Dawley rats. TMG dissolved in physiological saline was injected intraperitoneally 0.5 h before the aspirin administration. The intragastric administration of acidified aspirin induced hyperemia and hemorragic erosions in rat stomach. The increase in total area of gastric erosions was reduced by pretreatment with TMG in a dose-dependent manner. The increases of thiobarbituric acid-reactive substances (TBA-RS) and myeloperoxidase (MPO) activity 3 h after aspirin administration were significantly inhibited by pretreatment with TMG. The gastric concentration of cytokine-induced neutrophil chemoattractants-1 (CINC-1) increased after aspirin administration, and the increase was also inhibited by pretreatment with TMG. These results suggest that TMG is effective for the treatment of aspirin-induced gastric injury. This anti-inflammatory effect of TMG seems to be related to impairment of lipid peroxidation, neutrophil function and cytokine production in gastric mucosa.
Isozaki
Yutaka
Y
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Yoshida
Norimasa
N
Ichikawa
Hiroshi
H
Kuroda
Masaaki
M
Kokura
Satoshi
S
Naito
Yuji
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013272:Stomach Diseases / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*
C106323:2-(glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002839:Chromans; C513297:Cxcl1 protein, rat; D006027:Glycosides; D036341:Intercellular Signaling Peptides and Proteins; D008054:Lipid Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D009195:Peroxidase; D001241:Aspirin