Effect of 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors (statins) on tissue paraoxonase 1 and plasma platelet activating factor acetylhydrolase activities.
The authors investigated the effect of pravastatin and fluvastatin on paraoxonase 1 (PON1) activity in plasma, liver, heart, and kidney, as well as on plasma platelet activating factor acetylhydrolase (PAF-AH) in the rat. The animals received pravastatin at doses of 4 and 40 mg/kg/d or fluvastatin at doses of 2 or 20 mg/kg/d for 3 weeks. Fluvastatin (20 mg/kg/d) reduced plasma PON1 activity toward paraoxon and phenyl acetate by 23.6% and 17.4%, respectively. The lower dose of this drug as well as both doses of pravastatin had no effect on plasma PON1. PON1 activity toward paraoxon in the liver of rats treated with 20 mg/kg/d fluvastatin was 27.5% lower than in the control group, and the activity toward phenyl acetate was reduced by 25.4% and 35.9% in rats receiving 2 and 20 mg/kg/d of this drug, respectively. Fluvastatin at 2 and 20 mg/kg/d also decreased cardiac PON1 by 31.3% and 27.3%, respectively. Both statins reduced PON1 activity in the renal cortex and medulla. Statins had no effect on plasma PAF-AH. It is concluded that fluvastatin reduces PON1 activity more efficiently than does pravastatin. Reducing effect on PON1 may negatively modulate atheroprotective potential of statins and may contribute to differences in antiatherosclerotic properties of different drugs in this group.
Bełtowski
Jerzy
J
Department of Paraphysiology, Medical University, Lublin, Poland. jerzybel@hotmail.com
Wójcicka
Grazyna
G
Jamroz
Anna
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000818:Animals; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000097:blood / Q000494:pharmacology*; D000077340:Fluvastatin; D006321:Heart / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D017035:Pravastatin / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D002784:Cholesterol; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase; D017035:Pravastatin