V. Z. Lankin

Role of antioxidant enzymes and antioxidant compound probucol in antiradical protection of pancreatic beta-cells during alloxan-induced diabetes.

The severity of disturbances in carbohydrate metabolism in rats with alloxan-induced diabetes depended on activity of antioxidant enzymes in the target organ (pancreas). Damage to the pancreas is related to intensive generation of reactive oxygen species, free radicals, and lipid peroxides. Alloxan-induced diabetes in rats is a free radical disease, which in vivo serves as a useful model for the search for pharmacological preparations with antiradical and antioxidant properties. The antioxidant compound probucol indirectly increased activity of antioxidant enzymes in the pancreas and prevented the development of alloxan-induced diabetes in rats. Our results indicate that different sensitivity of laboratory animals of various species (rats and guinea pigs) to the influence of alloxan is associated with abnormal variations in activity of enzymes utilizing reactive oxygen species and lipid peroxides in mammalian pancreatic cells.

Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver

We studied the effects of two inhibitors of β-hydroxy-β-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 β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Oxidation of Plasma Low-Density Lipoproteins from Coronary Patients with Various Forms of Hypercholesterolemia

The duration of lag-phase of copper-induced free-radical oxidation of atherogenic LDL isolated from the plasma of coronary patients without hypercholesterolemia virtually does not differ from that of normal human LDL. On the other hand, lag-phase of plasma LDL oxidation was minimal in coronary patients with primary hypercholesterolemia without familial history and especially in patients with familial hypercholesterolemia. This can be attributed to sharply decreased content of natural lipid antioxidants in LDL of patients with familial hypercholesterolemia. However, therapy with natural antioxidant vitamin E did not modulate oxidizability of these LDL. By contrast, therapy with β-hydroxy-β-methylglutaryl-coenzyme A reductase inhibitor suppressing biosynthesis of ubiphenol Q induced sharp accumulation of lipoperoxides in LDL in vivo. These data suggest that reduced form of ubiquinone Q is the main antioxidant protecting LDL from free-radical oxidation.

Effect of Ubiquinone Q10 and Antioxidant Vitamins on Free Radical Oxidation of Phospholipids in Biological Membranes of Rat Liver

We studied the effects of 30-day peroral treatment with β-carotene, a complex of antioxidant vitamins (vitamins C and E and provitamin A) and selenium, and solubilized ubiquinone Q10 on the antioxidant potential in rat liver (ascorbate-dependent free radical oxidation of unsaturated membrane phospholipids). β-Carotene irrespective of the administration route increased antioxidant potential of the liver by 2–3.5 times. The complex of antioxidant vitamins and selenium increased this parameter by more than 15 times. Antiradical activity in rat liver was extremely high after administration of solubilized ubiquinone Q10 (increase by more than by 36 times). It can be expected that reduced ubiquinone Q10in vivo should produce a more pronounced protective effect due to activity of the system for bioregeneration of this natural antioxidant.

A Complex of Antioxidant Vitamins Effectively Inhibits Free-Radical Oxidation of LDL Phospholipids in Blood Plasma and Membrane Structures of the Liver and Myocardium

Antioxidant effect of a complex preparation including antioxidant vitamins C, E, provitamin A and selenium was studied on the model of Cu2+-initiated free-radical oxidation of LDL isolated from human blood plasma. The antioxidant effect of combined administration of α-tocopherol+ascorbic acid and α-tocopherol+β-carotene is far more pronounced that the antioxidant effect of individual components of these cocktails. Moreover, in the model system the combined action of all antioxidant components completely inhibited free-radical oxidation of LDL. A 30-day course of peroral administration of antioxidant vitamin cocktail and selenium to rats pronouncedly enhanced the antioxidant potential of liver and completely suppressed free-radical processes in the myocardium. It is suggested that preparations containing antioxidant vitamins and selenium can be perspective for prevention and complex therapy of atherosclerosis.

Complex of Vitamins and Antioxidants Protects Low-Density Lipoproteins in Blood Plasma from Free Radical Oxidation and Activates Antioxidants Enzymes in Erythrocytes from Patients with Coronary Heart Disease

We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively.

In vivo intensification of free-radical oxidation of low-density lipoproteins in the plasma of patients with coronary heart disease treated with β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitor pravastatin and inhibition of lipid peroxidation with ubiquinone Q10

Pravastatin, an inhibitor of β-hydroxy-β-methylglutaryl coenzyme A reductase, the key enzyme of cholesterol biosynthesis,in vivo elevated the content of primary and secondary products of free-radical oxidation in low-density lipoproteins in patients with coronary heart disease, while combined treatment with pravastatin and ubiquinone Q10 sharply decreased this parameter. Ubiquinone Q10 prevented pravastatin-induced inhibition of antioxidant enzymes superoxide dismutase and lipid peroxidase utilizing reactive oxygen species in the blood. These data indicate that ubiquinone Q10 would be appropriate for use in combination with statins, inhibitors of β-hydroxy-β-methylglutaryl coenzyme A reductase, for the therapy of patients with coronary heart disease.

Enhanced blood activity of selenic glutathione peroxidase in patients with coronary heart disease after treatment with selenium-containing antioxidant preparation adrusen zinco

This study analyzed the effects of nutriceutic Adrusen Zinco containing vitamin E and prosthetic groups of antioxidant enzymes (selenium, copper, zinc) on the parameters of free radical oxidation of blood lipids in patients with coronary heart disease and hypercholesterolemia. Adrusen Zinco considerably increased activity of erythrocyte and serum selenic glutathione peroxidase as soon as after 1-month treatment, while erythrocyte SOD activity significantly increased only after 2 months.