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.
Department of Analytical Chemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611, Japan. t-obata@pha.ohu-u.ac.jp
Toshio
T
Obata
Hidetoshi
H
Yonemoti
Masahiro
M
Aomine
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002396:Catechols / Q000378:metabolism; D003300:Copper / Q000633:toxicity; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006321:Heart / Q000187:drug effects; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D002396:Catechols; D005229:Fatty Acids, Monounsaturated; D062385:Hydroxybenzoates; D007211:Indoles; D008077:Lipoproteins, LDL; D017665:Hydroxyl Radical; D000077340:Fluvastatin; C009135:2,3-dihydroxybenzoic acid; D003300:Copper