Intensification of free radical oxidation of low-density lipoproteins in the plasma of patients with ischemic heart disease receiving beta-hydroxy-beta-methylglutaryl-coenzyme A reductase inhibitor cerivastatin and inhibition of low-density lipoprotein peroxidation with antioxidant probucol.
Inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (statins) decrease cholesterol content in atherogenic low-density lipoproteins in patients with coronary heart disease and hypercholesterolemia, but inhibited biosynthesis of ubiquinone Q10 protecting low-density lipoproteins from free radical oxidation. Cerivastatin in a daily dose of 0.4 mg markedly increased the content of lipid peroxides in low-density lipoproteins. However, complex therapy with cerivastatin and antioxidant probucol (250 mg/day) was accompanied by a sharp decrease in the content of lipid peroxides in low-density lipoproteins in patients with coronary heart disease in vivo. These data indicate that antioxidant agents should be used in combination with inhibitors of beta-hydroxy-beta-methylglutaryl-coenzyme A reductase (hypolipidemic preparations) for the therapy of patients with coronary heart disease.
Lankin
V Z
VZ
Laboratory of Biochemistry of Free Radical Processes, A. L. Myasnikov Institute of Cardiology, Russian Research-and-Production Center for Cardiology, Russian Ministry of Health, Moscow.
Tikhaze
A K
AK
Konovalova
G G
GG
Tutunov
V S
VS
Medvedeva
N V
NV
Kotkina
T I
TI
Kukharchuk
V V
VV
Belenkov
Yu N
YN
D000975:Antioxidants / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D003067:Coenzymes; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood*; D010100:Oxygen / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D010919:Placebos; D011341:Probucol / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011897:Random Allocation; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D008078:Cholesterol, LDL; D003067:Coenzymes; D004791:Enzyme Inhibitors; D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D010545:Peroxides; D010919:Placebos; D011725:Pyridines; D014451:Ubiquinone; D002784:Cholesterol; C086276:cerivastatin; C024989:coenzyme Q10; D011341:Probucol; D010100:Oxygen