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(+).