Abstract
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.
MeSH terms
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Alanine Transaminase / blood
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Allopurinol / therapeutic use
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Animals
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Antioxidants / therapeutic use*
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Ascorbic Acid / metabolism
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Aspartate Aminotransferases / blood
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Catalase / metabolism
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Chemical and Drug Induced Liver Injury / drug therapy
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Chemical and Drug Induced Liver Injury / etiology
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Chemical and Drug Induced Liver Injury / metabolism*
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Galactosamine / toxicity*
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Glutathione / metabolism
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Glutathione Peroxidase / metabolism
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Lipid Peroxidation
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Liver / drug effects*
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Liver / enzymology
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Male
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Neutrophils / enzymology
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Neutrophils / physiology
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Peroxidase / metabolism
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Phospholipid Hydroperoxide Glutathione Peroxidase
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Rats
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Rats, Wistar
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Reactive Oxygen Species / toxicity*
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Superoxide Dismutase / metabolism
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Uric Acid / blood
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Xanthine Dehydrogenase / metabolism
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Xanthine Oxidase / antagonists & inhibitors
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Xanthine Oxidase / metabolism*
Substances
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Antioxidants
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Reactive Oxygen Species
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Uric Acid
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Allopurinol
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Galactosamine
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Phospholipid Hydroperoxide Glutathione Peroxidase
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Catalase
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Peroxidase
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Glutathione Peroxidase
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Superoxide Dismutase
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Xanthine Dehydrogenase
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Xanthine Oxidase
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Aspartate Aminotransferases
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Alanine Transaminase
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Glutathione
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Ascorbic Acid