Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator.
The relationship between the changes of active oxygen metabolism and blood flow and the formation, progression, and recovery of lesions was examined in the gastric mucosa of rats treated once with compound 48/80, a mast cell degranulator. Gastric mucosal lesions appeared 0.5 hr after compound 48/80 treatment, became worst at 3 hr, and recovered fairly well at 12 hr. Increases in gastric mucosal lipid peroxide content and xanthine oxidase and myeloperoxidase activities and decreases in gastric mucosal vitamin E and hexosamine contents and Se-dependent glutathione peroxidase activity occurred with the formation and progression of gastric mucosal lesions. These changes were attenuated with the recovery of the lesion. Gastric mucosal nonprotein SH content decreased with the formation of gastric mucosal lesions, and this decreased SH content returned to near the original level with lesion progression. No changes in gastric mucosal superoxide dismutase and catalase activities occurred with the formation, progression, and recovery of gastric mucosal lesions. Gastric mucosal blood flow decreased with the formation of gastric mucosal lesions, and this decreased blood flow recovered with lesion progression. Serum serotonin concentration, an index of mast cell degranulation, increased with the formation of gastric mucosal lesions, and this increased serotonin level was attenuated with lesion progression and recovery. Pretreatment with ketotifen, a connective tissue mast cell stabilizer, prevented the formation of gastric mucosal lesions, the increases of gastric mucosal lipid peroxide content, xanthine oxidase and myeloperoxidase activities, and serum serotonin level; and the decreases of gastric mucosal nonprotein SH content, glutathione peroxidase activity, and blood flow found at 0.5 hr after compound 48/80 treatment. These results indicate that the changes of gastric mucosal active oxygen metabolism and blood flow are closely related to the formation, progression, and recovery of gastric mucosal lesions in rats with a single compound 48/80 treatment. The present results also suggest that this compound 48/80-induced gastric mucosal injury could be a kind of ischemia-reperfusion-induced injury occurring through degranulation of connective tissue mast cells.
Ohta
Y
Y
Department of Biochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
Kobayashi
T
T
Nishida
K
K
Ishiguro
I
I
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000503:physiopathology; D005979:Glutathione Peroxidase / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D007665:Ketotifen / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000139:chemically induced* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000633:toxicity
D006595:Hexosamines; D008054:Lipid Peroxides; D011743:Pyrimidines; D013438:Sulfhydryl Compounds; D014810:Vitamin E; D003189:p-Methoxy-N-methylphenethylamine; C087838:MAR 99; D009195:Peroxidase; D005979:Glutathione Peroxidase; D014969:Xanthine Oxidase; D007665:Ketotifen