Xanthine oxidase-derived reactive oxygen metabolites contribute to liver necrosis: protection by 4-hydroxypyrazolo[3,4-d]pyrimidine.
Xanthine oxidase (XO) generates reactive oxygen metabolites (ROM) as a by-product while catalyzing their reaction. The present study implicates these ROM in the pathogenesis of liver necrosis produced in rats by the intraperitoneal administration of thioacetamide (TAA; 400 mg/kg b.wt.). After 16 h of TAA administration, the activity of rat liver XO increased significantly compared to that of the control group. At the same time, the level of serum marker enzymes of liver necrosis (aminotransferases and alkaline phosphatase) and tissue malondialdehyde content also increased in TAA treated rats. Tissue malondialdehyde concentration is an indicator of lipid peroxidation and acts as a useful marker of oxidative damage. Pretreatment of rats with XO inhibitor (4-hydroxypyrazolo[3,4-d]pyrimidine; allopurinol (AP)) followed by TAA could lower the hepatotoxin-mediated rise in malondialdehyde level as well as the level of marker enzymes associated with liver necrosis. The survival rate also increased in rats given AP followed by the lethal dose of TAA. In either case, the effect of AP was dose-dependent. Results presented in the paper indicate that increased production of XO-derived ROM contributes to liver necrosis, which can be protected by AP.
Ali
S
S
Department of Biochemistry, Faculty of Science, Hamdard University, New Delhi, India. ali_shakir@hotmail.com
Diwakar
G
G
Pawa
S
S
Siddiqui
M R
MR
Abdin
M Z
MZ
Ahmad
F J
FJ
Jain
S K
SK
D000469:Alkaline Phosphatase / Q000097:blood; D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000032:analysis; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D009336:Necrosis; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013853:Thioacetamide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000637:Transaminases / Q000097:blood; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013853:Thioacetamide; D008315:Malondialdehyde; D000493:Allopurinol; D014969:Xanthine Oxidase; D000637:Transaminases; D000469:Alkaline Phosphatase; D005978:Glutathione