Protective effect of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on MPP +-induced hydroxyl radical in the rat striatum

Abstract

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/μl/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 μM) 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 +.