Role of active oxygen, lipid peroxidation, and antioxidants in the pathogenesis of gastric mucosal injury induced by indomethacin in rats.
The roles of active oxygen, lipid peroxidation, and the antioxidative defence mechanism in gastric mucosal injury induced by treatment with indomethacin in rats were investigated. The total area of gastric erosions and concentration of lipid peroxides in the gastric mucosa increased with time after administration of indomethacin (20 mg/kg, orally). The alpha-tocopherol:total cholesterol ratio in serum was significantly decreased and the activity of glutathione peroxidase, an important enzyme to scavenger of lipid peroxides, was inhibited by the administration of indomethacin. Treatments with superoxide dismutase and catalase inhibited the increases in gastric mucosal erosions and lipid peroxides in the gastric mucosa, and the reduction of serum alpha-tocopherol. Treatment with these scavengers did not improve the decreased glutathione peroxidase activity. These findings suggest that active oxygen species and lipid peroxidation play an important part in the pathogenesis of gastric mucosal injury induced by indomethacin, and that the decreased glutathione peroxidase activity aggravated the injury due to accelerated accumulation of hydrogen peroxide and lipid peroxides in the gastric mucosal cell.
Yoshikawa
T
T
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Naito
Y
Y
Kishi
A
A
Tomii
T
T
Kaneko
T
T
Iinuma
S
S
Ichikawa
H
H
Yasuda
M
M
Takahashi
S
S
Kondo
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D000975:Antioxidants; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; D007213:Indomethacin; D004121:Dimethyl Sulfoxide