Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effect of fluvastatin sodium (fluvastatin) and pravastatin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, on the formation of thiobarbituric acid reactive substances both in vivo and in vitro in rat liver microsomes and on active oxygen species. Oral administration of fluvastatin at low doses (3.13 and 6.25 mg/kg) inhibited the formation of thiobarbituric acid reactive substances in rat liver microsomes, but high doses (12.5 and 25 mg/kg) did not change the formation of thiobarbituric acid reactive substances. Fluvastatin at any dose used had no effect on the content of cytochrome P-450 and the activity of NADPH-cytochrome P-450 reductase. In in vitro experiments, concentrations of fluvastatin ranging from 1 x 10(-6) - 1 x 10(-4) M markedly inhibited NADPH-dependent lipid peroxidation in liver microsomes, but pravastatin weakly inhibited lipid peroxidation. The order of magnitude of inhibition of each drug on in vitro lipid peroxidation was butylated hydroxytoluene > probucol > or = fluvastatin > pravastatin. Moreover, fluvastatin chemically scavenged active oxygen species such as hydroxyl radicals and superoxide anion generated by the Fenton reaction and by the xanthine-xanthine oxidase system, respectively, but pravastatin showed no scavenging of superoxide anion. These results indicate that the suppression of in vivo and in vitro lipid peroxidation in liver microsomes may be, at least in part, due to the scavenging by fluvastatin of free radicals.
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PMID:Fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, scavenges free radicals and inhibits lipid peroxidation in rat liver microsomes. 985 51

We previously reported that fluvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, a strong lipid lowering drug, exerted an anti-atherosclerotic effect at doses insufficient to lower serum lipids in cholesterol fed rabbits. The evidence demonstrated that the superoxide anions from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase plays a critical role in several steps in the development of atherosclerosis. This study was designed to determine the effects of HMG-CoA reductase inhibitors on the production of the superoxide anions of NADPH oxidase in isolated rat peritoneal neutrophils. Fluvastatin (1-10 microM) decreased phorbol 12-myristate 13-acetate (PMA, 10 nM)-dependent reactive oxygen species (ROS) generation in a concentration-dependent manner. It also (10 microM) decreased PMA-dependent O(2) consumption of the rat neutrophils. These effects were reversed by the addition of mevalonate, a metabolite in the HMG-CoA reductase pathway. Treatment with pravastatin did not show any significant changes. Fluvastatin (10 microM) decreased ROS, such as hydroxyl radicals and superoxide anions generated by the Fenton reaction, and by the xanthine-xanthine oxidase system. Rats were treated with either fluvastatin (5 mg/kg per day, p.o.) or pravastatin (5 mg/kg per day, p.o.) for 1 week. Treatment with fluvastatin decreased the PMA-dependent ROS generation. The fluvastatin induced effect on the PMA-dependent ROS generation was reversed by the combined administration with 40 mg/kg mevalonate per day. The antioxidative effect of fluvastatin was thought to have caused not only the scavenging action of the radicals but also to have inhibited ROS generation by inhibiting the NADPH oxidase activity. This antioxidative potential of fluvastatin via the inhibition of NADPH oxidase activity may be profitable in preventing atherosclerosis.
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PMID:Antioxidative potential of fluvastatin via the inhibition of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. 1280 93