Protective effect of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on MPP(+)-induced hydroxyl radical in the rat striatum.
We examined whether fluvastatin, an inhibitor of low-density lipoprotein (LDL) oxidation, can resist 1-methyl-4-phenylpyridine (MPP(+))-induced hydroxyl radical generation (.OH) in the extracellular fluid of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/microliter/min) was infused through a microdialysis probe to detect the generation of.OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP(+) (5 mM; total dose 75 nmol) clearly produced an increase in.OH formation. However, fluvastatin (100 microM) reduced the.OH formation by the action of MPP(+). These results indicated that fluvastatin, a potent inhibitor of LDL oxidation, may resist the formation of.OH products of MPP(+).
Obata
T
T
Department of Pharmacology, Oita Medical University, 1-1, Hasama-machi, Oita, Japan. tobata@oita-med.ac.jp
Yamanaka
Y
Y
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D003300:Copper / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D016166:Free Radical Scavengers / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D008995:Monoamine Oxidase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D005229:Fatty Acids, Monounsaturated; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008077:Lipoproteins, LDL; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; C099252:oxidized low density lipoprotein; D017665:Hydroxyl Radical; D000077340:Fluvastatin; C009135:2,3-dihydroxybenzoic acid; D003300:Copper; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine