Biomedical subjects

A K Tikhaze

Publications and source records attributed to A K Tikhaze.

At least 19 recordsLinked to original sources

PubMed2006

[Effect of ubiquinone on contractile function and antioxidant status of the myocardium in spontaneously hypertensive rats].

During the period of aging of spontaneously hypertensive rats (SHR) between 6 and 13 weeks the systolic arterial pressure increased from 131+/-2 up to 176+/-3 mm Hg while in the control group of WKY rats it reached 122+/-2 mmHg. The hypertension was combined with myocardial hypertrophy -- the relative weight of SHR heart was 24% higher. The contractile myocardial function of the isolated isovolumic heart of SHR group did not differ from WKY group in a wide range of coronary perfusion rates. During oxidative stress induced by 40-min intracoronary introduction of H(2)O(2) function of hypertrophied SHR hearts fell significantly deeper. This coincided with decreased myocardial activity of superoxide dismutase and glutathione peroxidase by 29-30%, and increased catalase activity by 18%. The rate of generation of active forms of oxygen (hydroxyl radicals HO(.-)) in mitochondria from SHR hearts was higher as compared with WKY. Thus, the development of hypertension was combined with decreased antioxidant protection of the myocardium. The addition of ubiquinone to drinking water (approximately 10 mg/kg/day) for 6 weeks did not affect arterial pressure level, but was associated with two times lesser degree of myocardial hypertrophy. The hearts of SHR that received ubiquinone differed from those not treated with ubiquinone by increased maximal level of myocardial contractile function, and by improved myocardial relaxability and distensibility. After administration of H(2)O(2), myocardial function of SHR was kept on higher level. That was combined with less myocardial oedema, better preservation of antioxidant enzymes and reduced rate of succinate-dependent generation of superoxide radicals in mitochondria from hearts of ubiquinone treated SHR. The results have shown, that administration of ubiquinone to rats with hereditary hypertension reduces degree of myocardial hypertrophy, improves functional properties of the myocardium, promotes effective protection of antioxidant enzymes and increases the resistance of the cardiac muscle to oxidative stress.

Animals↗

PubMed2005

Low daily dose of antioxidant probucol decreases incidence and severity of restenosis after transluminal coronary balloon angioplasty.

Antioxidant probucol in both high (1000 mg) and low (250 mg) daily doses effectively reduced manifestations of oxidative stress in patients with atherosclerosis (assessed by in vivo accumulation of lipoperoxides in atherogenic LDL). When probucol was administered in a dose of 250 mg/day for 7-10 days before transluminal balloon coronary angioplasty and then for 6 months after surgery, the incidence of restenosis decreased to 25% compared to 45% in the control (without probucol therapy). In the group of operated patients receiving probucol (250 mg/day for 6 months) the minimal artery lumen was significantly higher, and the degree of artery occlusion significantly lower than in the control group not treated with probucol.

Angioplasty, Balloon, Coronary↗

PubMed2005

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 Fe(2+) 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.

Adult↗

PubMed2005

Effect of ubiquinone Q(10) 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 beta-carotene, a complex of antioxidant vitamins (vitamins C and E and provitamin A) and selenium, and solubilized ubiquinone Q(10) on the antioxidant potential in rat liver (ascorbate-dependent free radical oxidation of unsaturated membrane phospholipids). beta-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 Q(10) (increase by more than by 36 times). It can be expected that reduced ubiquinone Q(10) in vivo should produce a more pronounced protective effect due to activity of the system for bioregeneration of this natural antioxidant.

Animals↗

PubMed2005

Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q10.

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium. Changes in the antioxidant status of the myocardium induced by long-term addition of coenzyme Q(10) into food was accompanied by decrease in the negative inotropic effect of H2O2, whereas the levels of superoxide dismutase and glutathione peroxidase after oxidative stress were virtually unchanged. The activities of these enzymes displayed a high positive correlation with the cardiac function. The findings suggest that coenzyme Q(10) should increase resistance of the myocardium to oxidative stress not only by a direct antioxidant mechanism but also indirectly, due to increased protection of antioxidant enzymes.

Animals↗

PubMed2004

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.

Animals↗

PubMed2004

Protection of rat myocardium by coenzyme Q during oxidative stress induced by hydrogen peroxide.

Ubiquinone Q(10) (coenzyme Q) is an important component of the mitochondrial electron transport chain and an antioxidant. The purpose of this work was to find out whether an increase in the level of coenzyme Q in the heart changes its maximal working capacity and resistance to oxidative stress. Male Wistar rats were treated with coenzyme Q (10 mg/kg body weight per day) for six weeks, and this increased its content in the myocardium by 63%. The myocardial content of malonic dialdehyde and activities of key antioxidant enzymes were unchanged, except nearly 2.5-fold decrease in the activity of superoxide dismutase. The maximal working capacity of the isolated isovolumic heart did not change, but under conditions of oxidative stress induced by 45-min infusion of hydrogen peroxide (70 micro M) into coronary vessels the contractile function of these hearts decreased significantly more slowly. This was associated with less pronounced lesions in the ultrastructure of cardiomyocytes and lesser disorders in the oxidative metabolism of mitochondria that suggested increased antioxidant protection of the myocardium.

Animals↗

PubMed2004

[Antioxidants in complex therapy of atherosclerosis: pro et contra].

The review contains current insights into the role of free radical processes in formation of oxidative stress in atherosclerosis and its relevance to therapy and prevention. Data of epidemiological studies evidence for existence of correlations between blood plasma content of antioxidant vitamins and presence of signs of atherosclerosis. However mostly positive data on the use of antioxidants in various animal experimental models of atherosclerosis contrast with equivocal results of therapeutic application of antioxidant vitamins in humans. Possible causes for this controversy have been choice of suboptimal combinations of components, extremely high concentrations of consumed substances, lack of biochemical testing of baseline antioxidant status and its changes in the process of therapy. The authors of the review suggest novel approaches to planning of clinical trials of antioxidant vitamins.

Animals↗

PubMed2004

[Experimental and clinical assessment of antioxidant efficacy of multicomponent antioxidant medication].

AIM: To study an antioxidant action of antioxidant vitamins (vitamins C, E and provitamin A) in vitro and in vivo. MATERIAL AND METHODS: The study was made of kinetic parameters of copper-initiated free radical oxidation (FRO) of low density lipoproteins (HDLP) in human blood plasm, antioxidant potential of rat liver and myocardium, the level of FRO products in HDLP and activity of glutathione peroxidase in erythrocytes of 31 males aged 40-64 years with coronary heart disease (CHD). RESULTS: An antioxidant action of the combinations alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-carotin was much more potent than that of each of the component alone. The whole complex of the antioxidants completely suppressed FRO of HDLP in the model system. Feeding rats for 30 days with a complex of antioxidant vitamins and selenium produced a sharp enhancement of the antioxidant potential of the liver and a complete suppression of free radical processes in the myocardium. If this complex was given to CHD patients for 2 months, it sharply reduced the amount of FRO primary and secondary products in blood plasm LDLP in growing activity of erythrocytic selenium-containing glutathione peroxidase. CONCLUSION: The scheme is proposed for objective experimental assessment of antioxidant efficacy of multicomponent antioxidant medication in laboratory and clinical trials.

Adult↗

PubMed2003

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 Cu(2+)-initiated free-radical oxidation of LDL isolated from human blood plasma. The antioxidant effect of combined administration of alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-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.

Animals↗

PubMed2003

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 beta-hydroxy-beta-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.

Adult↗

PubMed2003

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.

Aged↗

PubMed2003

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.

Adult↗

PubMed2002

Modeling the cascade of enzymatic reactions in liposomes including successive free radical peroxidation, reduction, and hydrolysis of phospholipid polyenoic acyls for studying the effect of these processes on the structural-dynamic parameters of the membranes.

Studies of the effect of primary products of free radical lipid peroxidation (LPO) on the structural-dynamic parameters of natural lipid-protein supramolecular complexes (biomembranes and blood serum lipoproteins) using standard inducers of radical processes in vitro (azo-initiators, transition metal ions, flavin oxidases, etc.) are impossible because of simultaneous production of numerous secondary LPO products that can induce structural changes. The data obtained suggest that phospholipid liposome microviscosity, as assessed by the extent of eximerization of the fluorescent probe pyrene, may significantly differ when oxidation is induced by animal C-15 lipoxygenase (yielding acylhydroperoxides only) and Fe(2+)-ascorbate system (resulting in simultaneous accumulation of primary and secondary LPO products). It is also shown that liver glutathione S-transferase can effectively reduce hydroperoxy-acyls in phospholipid liposomes and liver microsomes without their preliminary hydrolysis with phospholipase A(2). An enzymatic system is proposed for a cascade of enzymatic reactions simulating lipohydroperoxide metabolism in living cells, including successive free radical oxidation of phosphatidylcholine polyenoic acyls, reduction of their hydroperoxy-derivatives, and hydrolysis of fatty acid residues in the course of catalysis mediated by animal C-15 lipoxygenase, glutathione S-transferase, and phospholipase A(2), respectively.

Animals↗

PubMed2002

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.

Antioxidants↗

PubMed2001

Inhibitor of beta-hydroxy-beta-methylglutaryl coenzyme A reductase decreases energy supply to the myocardium in rats.

Hypocholesterolemic preparations, inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl coenzyme A reductase (statins), block the synthesis of ubiquinone Q10, intermediate electron carrier in the mitochondrial respiratory chain. This should decrease energy supply to tissues. Daily peroral administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor simvastatin (24 mg/kg perorally) for 30 days had no effect on the contents of macroergic phosphates (ATP and creatine phosphate) in the liver, but decreased these parameters in the myocardium.

Adenosine Diphosphate↗

PubMed2000

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 licorice Glycyrrhiza 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 beta-carotene-containing preparations carinat and carinat CD. Parapharmaceutics containing both licorice Glycyrrhiza glabra root powder and beta-carotene (carinat forte) markedly increased antioxidant activity of the liver.

Animals↗

PubMed2000

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

The effects of pretreatment with beta-carotene-containing preparation carinat on the development of renal tumors in rats receiving single intravenous injection of chemical carcinogen 3-(1-alpha-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 producing in 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 beta-carotene.

Animals↗