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.

Nardostachys jatamansi protects against liver damage induced by thioacetamide in rats.

Nardostachys jatamansi is a medically important herb of Indian origin used for centuries in Ayurvedic and Unani systems of medicine for the treatment of various ailments. In the present paper, a 50% ethanolic extract of the rhizomes of N. jatamansi is shown to possess hepatoprotective activity. Pretreatment of rats with the extract (800 mg/kg body wt, orally) for three consecutive days significantly ameliorated the liver damage in rats exposed to the hepatotoxic compound thioacetamide. Elevated levels of serum transaminases (aminotransferases) and alkaline phosphatase, observed in thioacetamide alone treated group of animals, were significantly lowered in N. jatamansi pretreated rats. Pretreatment of the animals with the extract also resulted in an increase in survival in rats intoxicated with LD90 dose of the hepatotoxic drug.

Paraquat induces different pulmonary biochemical responses in Wistar rats and Swiss mice.

The paper presents results showing differential response to paraquat toxicity in Wistar rats and Swiss strain of mice. Paraquat-induced pulmonary biochemical responses in the two animal species were studied at different time point after giving a single intraperitoneal injection of the respective LD(10) doses of the herbicide paraquat to rats and mice. Paraquat induced different biochemical responses including different protective responses in the two animal species. As a protective response, NADPH-specific quinone reductase is induced in rats, while catalase is induced in mice. It is implied that an early induction of catalase in mice as opposed to rats may account for the resistance of Swiss mice to paraquat toxicity. Xanthine oxidase, which was induced in rats, remains unaffected in mice indicating that the enzyme contributes to paraquat toxicity only in Wistar rats. Time-course studies were also conducted to compare the differential responses of antioxidant enzymes and lipid peroxidation between the two species. The results of the study led us to suggest that the manifestation of paraquat toxicity involve distinct differences in early pulmonary biochemical responses in Wistar rats and Swiss mice.