Vulnerability of gastric mucosa to prednisolone in rats chronically exposed to cigarette smoke.
We examined gastric mucosal vulnerability in a rat model of chronic obstructive pulmonary disease (COPD). Male Wistar rats were exposed to cigarette smoke for 12 weeks (CSE rats), and on the last 4 days of exposure, prednisolone was given to induce gastric mucosal injury. Histopathology, pulmonary function, arterial blood gases, and levels of lipid peroxides (LPO), prostaglandin E(2) (PGE(2)), hypoxia-inducible factor 1 alpha subunit (HIF-1alpha), and vascular endothelial growth factor (VEGF) in gastric mucosa were examined. We also tested the effect of rebamipide on prednisolone-induced gastric lesions. In CSE rats, although no gastric lesions were detected, LPO, PGE(2), HIF-1alpha, and VEGF levels were higher than in control rats. Prednisolone induced gastric hemorrhagic lesions more readily in CSE rats than controls, with concomitant decrease in PaO(2) and increased levels of LPO, HIF-1alpha, and VEGF. Rebamipide reversed gastric lesions without affecting any parameters examined. CSE rats were found to be a useful animal model of COPD, and COPD appeared to render the gastric mucosa vulnerable to prednisolone.
Takeuchi
Yoshiaki
Y
Department of Internal Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
Takahashi
Maki
M
Fuchikami
Jun-ichi
J
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001784:Blood Gas Analysis; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D010438:Peptic Ulcer Hemorrhage / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011239:Prednisolone; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D012137:Respiratory System / Q000473:pathology; D012907:Smoking / Q000009:adverse effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000897:Anti-Ulcer Agents; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008054:Lipid Peroxides; D015363:Quinolones; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D011239:Prednisolone; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine