Trimetazidine as Indirect Antioxidant

One-month therapy with trimetazidine sharply decreased the content of free radical oxidation products, lipid peroxides and malonic dialdehyde, in atherogenic low-density lipoproteins in patients with coronary heart disease. Activity of glutathione peroxidase utilizing lipid peroxides in the plasma markedly increased during trimetazidine therapy. The data suggest that trimetazidine not directly interacting with free radicals attenuates the adverse effects of intensive free radical oxidation in coronary heart disease. This effect is mediated via activation of antioxidant enzymes, which diminishes negative consequences of ischemia.     

Does trimetazidine act as antioxidant?

Trimetazidine is 2-fold inferior to probucol in antioxidant activity measured using the model of copper-induced free radical oxidation of human plasma lipoproteins. EPR-spectroscopy shows that trimetazidine forms no free-radical intermediates in the presence of generated lipid alkoxyl or hydroxyl radicals, while probucol under these conditions forms phenoxyl radicals. Trimetazidine does not interact with superoxide radicals generated in the xanthinexanthine oxidase system, since it does not inhibit reduction of tetrazolium nitroblue. However, indirect effect of trimetazidine on free radical oxidation cannot be excludedin vivo. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 551–554, November, 1998     

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.     

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.     

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. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 3, pp. 277–279, March, 2000     

Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes

The duration of lag phase of ascorbate-dependent free radical oxidation of endogenous polyenic lipids in rat liver and myocardium considerably increased after oral administration of lacrinat containing licoriceGlycyrrhiza glabra root powder for 1 month. Lacrinat markedly decreased the content of lipid peroxides in rat liver.Ex vivo antioxidant effects of lacrinat in rat liver were comparable with those of β-carotene-containing preparations carinat and carinat CD. Parapharmaceutics containing both licoriceGlycyrrhiza glabra root powder and β-carotene (carinat forte) markedly increased antioxidant activity of the liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 56–58, July, 2000     

Antioxidant activity of parapharmaceutics containing natural inhibitors of free radical processes

The duration of lag phase of ascorbate-dependent free radical oxidation of endogenous polyenic lipids in rat liver and myocardium considerably increased after oral administration of lacrinat containing licoriceGlycyrrhiza glabra root powder for 1 month. Lacrinat markedly decreased the content of lipid peroxides in rat liver.Ex vivo antioxidant effects of lacrinat in rat liver were comparable with those of β-carotene-containing preparations carinat and carinat CD. Parapharmaceutics containing both licoriceGlycyrrhiza glabra root powder and β-carotene (carinat forte) markedly increased antioxidant activity of the liver. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 56–58, July, 2000     

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. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 2, pp. 176–179, February, 2000     

Antioxidant probucol as an effective scavenger of lipid radicals in low density lipoproteinsin vivo andin vitro

Probucol in concentrations of 10–15 μM effectively inhibits Cu²⁺-induced free radical oxidation of native low density lipoproteins and in concentration of 100 μM it inhibits lipoperoxide formation. The mean plasma concentration of probucol in patients receiving 250 mg of this drug is 25 μM. Both 250 and 1000 mg probucol daily during 3–6 month block the oxidation of isolated low density lipoproteins. Electron paramagnetic resonance spectrometry data showed that probucol incorporatedin vivo into lipoprotein particles interacts with lipid radicals yielding long-lived phenoxyradicals. Probucol can be used in complex therapy of atherosclerosis as an antioxidant drug and its dose required for lipoprotein protection against atherogenic modification can be decreased to 250 mg/day. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 8, pp. 186–189, August, 1999     

Antioxidant properties of thiamine

Thiamine (10⁻⁴–10⁻⁶ M) inhibits lipid peroxidation in rat liver microsome and free radical oxidation of oleic acidin vitro. Thiamine interacts with free radicals and hydroperoxides and is oxidized to thiochrome and thiamine disulfide. The antioxidant effect of thiamine is probably related to sucessive transfer of 2H⁺ from the NH₂ group of the pyrimidine ring and H⁺ from the thiazole ring (after its opening) to reactive substrates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 303–305, September, 2000     

Antioxidant properties of thiamine

Thiamine (10⁻⁴–10⁻⁶ M) inhibits lipid peroxidation in rat liver microsome and free radical oxidation of oleic acidin vitro. Thiamine interacts with free radicals and hydroperoxides and is oxidized to thiochrome and thiamine disulfide. The antioxidant effect of thiamine is probably related to sucessive transfer of 2H⁺ from the NH₂ group of the pyrimidine ring and H⁺ from the thiazole ring (after its opening) to reactive substrates. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 303–305, September, 2000     

ATP-sparing effect of histochrome in acute myocardial ischemia in patients with coronary heart disease

Afterin vitro ischemia, the content of adenosine triphosphate in myocardial bioptates from patients with heart diseases is reduced. This reduction is more pronounced in patients with coronary heart disease than in patients with rhythm disturbances. Administration of the antioxidant preparation histochrome to patients with coronary heart disease preserves ATP during ischemic exposure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 12, pp. 669–671, December, 1997     

Effect of ozone on lipid peroxidation in rat hearts isolated against the background of clinical death

Clinical death of outbred albino rats ensues after rapid blood loss due to a cut in the coronary coronary artery. Five minutes later, the isolated heart is perfused with ozonized Krebs-Henseleit solution. The activity of the antioxidant system in the heart is increased compared with that during routine oxygenation. The intensity of lipid peroxidation assessed by the intensity of chemiluminescence and the amount of lipid peroxidation products is significantly decreased during ozonization. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, № 2, pp. 161–163, February, 1996 Presented by B. A. Korolev, Member of the Russian Academy of Medical sciences     

Peculiarities of changes in the rate of cholesterol synthesis in lymphocytes and lipid and lipoprotein peripheral blood levels in patients with ischemic heart disease and hypercholesterolemia in the course of combined treatment with lovastatin and obsidan

It is shown that the level of total serum cholesterol dropped and the rate of cholesterol synthesis in lymphocytes remained unchanged after 12 months of lovastatin treatment (20 mg/day) in patients with coronary heart disease. The administration of lovastatin abolished the deleterious effect of obsidan on the blood lipid spectrum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, No 3, pp. 248–251, March, 1994 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

Interrelation between Compensation of Carbohydrate Metabolism and Severity of Manifestations of Oxidative Stress in Type II Diabetes Mellitus

Glycosylation end-products formed during diabetes mellitus promoted atherogenic oxidative modification of low-density lipoproteins. We evaluated the effects of compensation of carbohydrate metabolism and therapy with antioxidant probucol on parameters of free radical oxidation in patients with type II diabetes mellitus. Compensation of carbohydrate metabolism reduced manifestations of oxidative stress, which was manifested in accelerated enzymatic utilization of reactive oxygen species and lipid peroxides and decreased content of free radical oxidation products in low-density lipoproteins. In patients with type II diabetes mellitus combination therapy with antioxidant probucol decreased the severity of oxidative stress and stabilized carbohydrate metabolism without increasing the dose of hypoglycemic preparations.     

Oxidative Stress in Atherosclerosis and Diabetes

We measured the content of lipid peroxides in plasma LDL from patients with chronic CHD not accompanied by hypercholesterolemia; CHD and hypercholesterolemia; type 2 diabetes mellitus and decompensation of carbohydrate metabolism; and CHD, circulatory insufficiency, and type 2 diabetes mellitus (without hypercholesterolemia). The content of lipid peroxides in LDL isolated from blood plasma by differential ultracentrifugation in a density gradient was estimated by a highly specific method with modifications (reagent Fe²⁺ xylene orange and triphenylphosphine as a reducing agent for organic peroxides). The content of lipid peroxides in LDL from patients was much higher than in controls (patients without coronary heart disease and diabetes). Hypercholesterolemia and diabetes can be considered as factors promoting LDL oxidation in vivo. Our results suggest that stimulation of lipid peroxidation in low-density lipoproteins during hypercholesterolemia and diabetes is associated with strong autooxidation of cholesterol and glucose during oxidative and carbonyl (aldehyde) stress, respectively. These data illustrate a possible mechanism of the progression of atherosclerosis in patients with diabetes mellitus. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 7, pp. 48–51, July, 2005     

Dynamics of formation of primary and secondary lipid peroxidation products upon copper-dependent oxidation of low-density lipoproteins isolated from blood serum of patients with ischemic heart disease

The kinetics of copper-induced oxidation of lipids in serum low-density lipoproteins from healthy subjects and patients with ischemic heart disease and documented coronary atherosclerosis is studied. After a 4-h incubation with 40 μM CuSO₄, the oxidizability of patients' lipoproteins is higher, judging from the contents of diene conjugates and oxidation products reacting with thiobarbituric acid. Intergroup differences in the kinetics of the diene conjugate formation are revealed. Statistical analysis shows that in all studied individuals there is no relationship between the oxidizability of low-density lipoproteins and the cholesterol content in lipoproteins and serum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 32–36, July, 1996     

Beta-carotene-containing preparation carinat inhibits lipid peroxidation and development of renal tumors in rats treated with chemical carcinogen

The effects of pretreatment with β-carotene-containing preparation carinat on the development of renal tumors in rats receiving single intravenous injection of chemical carcinogen 3-(1-α-L-arabinopyranosyl)-1-methyl-1-nitrosourea were studied. Fourteen months after carcinogen administration, the degree of lipid oxidation in rat kidneys 2.5-fold surpassed that in animals receiving carinat in a dose producingin vivo antioxidant effect. Carinat decreased the total number of induced tumors and the incidence of mesenchymal renal tumors and suppressed the development of multiple tumors. The accumulation of lipoperoxides in the kidneys during carcinogenesis is associated with activation of free radical processes and carcinogen-induced inhibition of lipoperoxide enzymatic degradation and probably promotes renal malignancies due to co-carcinogenic action of these compounds. The data suggest that carinat-induced suppression of tumor development attests to antioxidant effects of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 95–97, July, 2000     

β-Carotene-containing preparation carinat inhibits lipid peroxidation and development of renal tumors in rats treated with chemical carcinogen

The effects of pretreatment with β-carotene-containing preparation carinat on the development of renal tumors in rats receiving single intravenous injection of chemical carcinogen 3-(1-α-L-arabinopyranosyl)-1-methyl-1-nitrosourea were studied. Fourteen months after carcinogen administration, the degree of lipid oxidation in rat kidneys 2.5-fold surpassed that in animals receiving carinat in a dose producingin vivo antioxidant effect. Carinat decreased the total number of induced tumors and the incidence of mesenchymal renal tumors and suppressed the development of multiple tumors. The accumulation of lipoperoxides in the kidneys during carcinogenesis is associated with activation of free radical processes and carcinogen-induced inhibition of lipoperoxide enzymatic degradation and probably promotes renal malignancies due to co-carcinogenic action of these compounds. The data suggest that carinat-induced suppression of tumor development attests to antioxidant effects of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 7, pp. 95–97, July, 2000     

Adaptation to periodic hypoxia and a diet supplemented with polyunsaturated class ω-3 fatty acids enhance the resistance of Ca2+ transport in the myocardial sarcoplasmic reticulum to free-radical oxidation

The relationship between the level of accumulation of lipid peroxidation products and the status of the Ca²⁺-transporting system in the sarcoplasmic reticulum of the rat myocardium is studied against the background of two cardioprotective factors, namely adaptation to periodic hypoxia and a diet enriched in polyunsaturated fatty acids of the ω-3 class. It is shown that the diet leads to an increase of level of lipid peroxidation products by 1.8 times in the heart and by 19 times in the liver, whereas a adaptation has no effect on the level of lipid peroxidation products in either of these organs. At the same time, the combined action of both factors considerably enhances the resistance of the myocardial Ca²⁺-transporting system to free radical-induced oxidation. Inin vitro experiments it is shown that adaptation to periodic hypoxia results in a more than twofold deceleration of Ca²⁺ transport inhibition during the oxidation induction by the Fe²⁺/ascorbate system; the diet causes a 3.5-fold deceleration of such inhibition. The results show that the accumulation of a high level of lipid peroxidation products is not always followed by damage to the Ca²⁺-transporting system in the myocardial sarcoplasmic reticulum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 7, pp. 42–45, July, 1995 Presented by G. N. Kryzhanovskii, Member of the Russian Academy of Medical Sciences