Xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats.
We examined whether xanthine oxidase (XO)-derived reactive oxygen species (ROS) contribute to the development of D-galactosamine (D-GaIN)-induced liver injury in rats. In rats treated with D-GaIN (500 mg/kg), liver injury appeared 6 h after treatment and developed until 24 h. Hepatic XO and myeloperoxidase activities increased 12 and 6 h, respectively, after D-GalN treatment and continued to increase until 24 h. D-GalN-treated rats had increased hepatic lipid peroxide (LPO) content and decreased hepatic reduced glutathione (GSH) and ascorbic acid contents and superoxide dismutase (SOD), catalase and Se-glutathione peroxidase (Se-GSHpx) activities at 24 h, but not 6 h, after treatment. Allopurinol (10, 25 or 50 mg/kg) administered at 6 h after D-GalN treatment attenuated not only the advanced liver injury and increased hepatic XO activity but also all other changes observed at 24 h after the treatment dose-dependently. These results suggest that XO-derived ROS contribute to the development of D-GaIN-induced liver injury in rats.
Ohta
Yoshiji
Y
Department of Chemistry, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. yohta@fujita-hu.ac.jp
Matsura
Tatsuya
T
Kitagawa
Akira
A
Tokunaga
Kenji
K
Yamada
Kazuo
K
D000410:Alanine Transaminase / Q000097:blood; D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D005688:Galactosamine / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D014527:Uric Acid / Q000097:blood; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014527:Uric Acid; D000493:Allopurinol; D005688:Galactosamine; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001205:Ascorbic Acid