Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.
We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.
Lankin
V Z
VZ
Laboratory for Biochemistry of Free Radical Processes, A. L. Myasnikov Institute of Cardiology. lankin@cardio.ru
Ivanova
M V
MV
Konovalova
G G
GG
Tikhaze
A K
AK
Kaminnyi
A I
AI
Kukharchuk
V V
VV
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D050356:Lipid Metabolism / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000494:pharmacology; D019821:Simvastatin / Q000494:pharmacology; D024505:Tocopherols / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*
D000975:Antioxidants; D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014815:Vitamins; D008148:Lovastatin; D019821:Simvastatin; D012643:Selenium; D001205:Ascorbic Acid; D024505:Tocopherols