The protective effect of fluvastatin on hydroxyl radical generation by inhibiting low-density lipoprotein (LDL) oxidation in the rat myocardium.

The present study examined the effect of fluvastatin on Cu(2+)-induced hydroxyl radical generation (*OH) in the extracellular fluid of rat myocardium using microdialysis technique (O system). Fluvastatin, an inhibitor of low-density lipoprotein (LDL) oxidation, was administered at a dose of 5.0 mg/kg/day i.p. for 4 weeks. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol/microl/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 myocardium. When CuSO(4) was infused through the microdialysis probe, CuSO(4) clearly produced an increase in *OH formation trapped as 2,3-DHBA (R(2)=0.983). However, when corresponding experiments were performed with fluvastatin (5.0 mg/kg/day i.p. for 4 weeks) pretreated animals, small increases in the level of 2,3-DHBA products were observed. When LDL is oxidized by Cu(2+), Cu(2+) can be reduced to Cu(1+) by LDL. Fenton-type reactions in the presence of Cu(1+) yields highly cytotoxic *OH. These results suggest that Cu(2+)-induced *OH generation may be reduced by inhibiting LDL oxidation with fluvastatin.