Inhibition of low density lipoprotein oxidation by melatonin

The antioxidant activity of the lipophilic hormone melatonin, “an ideal inhibitor of free radicals,” is studied in models of cellular (peritoneal mouse macrophages) and copper-induced oxidation of low density lipoproteins. Oxidative modification of low density lipoproteins is assessed by accumulation of thiobarbituric acid reactive substances and degradation of¹²⁵I-labeled lipoproteins in a fresh culture of macrophages. Melatonin inhibits in a dose-dependent manner cellular and copper-induced oxidation of lipoproteins and production of the superoxide anion radical by macrophages, the mean concentrations of 50% inhibition being 300, 1230, and 900 μM, respectively. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 10, pp. 399–402, October, 1996     

A probucol analog protects lipoproteins better than probucol

Using low density lipoproteins, the antioxidant activity of probucol and one of its analogs was examined, and the analog was found to be more effective than probucol in protecting these lipoproteins against oxidation. It is pointed out that the choice of particular probucol analogs for clinical treatment should depend on the antioxidant index of low density lipoproteins in the patient concerned. Translated formByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5, pp. 491–493, May 1995 Presented by E. I. Chazov, Member of the Russian Academy of Medical Sciences     

Chemiluminescence study of the contents of the products of Cu2+-induced lipid peroxidation in different fractions of human blood lipoproteins

It is demonstrated that the content of the primary products of lipid peroxidation reaches the maximum after about 1-h incubation with Cu²⁺ and then declines. At a Cu²⁺ concentration of about 10–15 μM, the content of lipid peroxidation products is maximal; it does not rise with a further increase in the Cu²⁺ concentration. Comparison of the kinetics of lipid peroxidation in different lipoprotein fractions shows that low density lipoproteins are much more strongly oxidized than high density lipoproteins. A strong positive correlation between the amplitude of the chemiluminescence burst and the diene conjugate content is established in 79 independent measurements. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 2, pp. 144–148, February, 1995     

Immunochemical analysis of common antigenic determinants in insulin and apoprotein B Molecules

A study is performed of the mechanism underlying stress diabetes, which develops in human beings and animals under stress. Dot-immunoanalysis shows the presence of common antigenic determinants in insulin, apoprotein B, and apoprotein B-containing low density and very low density lipoproteins isolated from human and rat serum. Electrophoresis, immunoelectroblotting, and immunoenzyme analysis reveal 5–6 peptides belonging to apoB, which specifically react with anti-insulin and anti-very low density lipoprotein antibodies. Insulinlike immunoreactivity is also identified in human serum supernatant obtained after precipitation of the total low density and very low density lipoprotein fraction and after removal all lipoproteins from it. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 258–261, September, 1994     

Polyunsaturated phosphatidylcholine micelle-induced decrease of atherogenicity of the serumin vitro

It is shown that polyunsaturated phosphatidylcholine administered in micelles stabilized by a plant-derived glycoside prevents the accumulation of cholesterol by cells incubated in atherogenic serum and, moreover, in certain cases causes a 1.4–1.5-fold drop of intracellular cholesterol as compared to control cells. The optimum antiatherogenic effect was achieved when using a micelle concentration of 100–200 μg/ml and an incubation time of at least 4 hours. The antiatherogenic effect was analogous to the effect of high density serum lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 5 pp. 497–501, May, 1995 Presented by Yu. M. Lopukhin, Member of the Russian Academy of Medical Sciences     

Estimation of Na-blocking efficiency of rihlocaine and its combinations with low-molecular-weight polymers on isolated rat cardiomyocytes

The effect of glucose-base polymers (dextrans with relative molecular weight 10, 40, and 70 kD) and vinylpyrrolidone (polyvinylpyrrolidone: 10, 24, and 40 kD) on changes in the sarcoplasmic Na⁺ concentration in stimulated cardiomyocytes (1.0 Hz, 10 msec, 60 mV) were examined. In the concentration range of 1–100 μM, the polymer preparations produced cardioprotective effect on cells incubated under hypoxic conditions; the effect depended on the nature and molecular weight of the polymer. Rihlocaine (25 μM) inhibits by 42% elevation of intracellular Na⁺ induced by plasma membrane depolarization. Dextran 40 is shown to significantly increase Na-blocking effect of rihlocaine. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 12, pp. 649–651, December, 1997     

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     

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     

Inhibition of human plasma ApoB-lipoproteins

The effects of astaxanthine and β-carotene on the oxidation of isolated human plasma apoB-lipoproteins induced by copper ions or hemin/hydrogen peroxide are studied. Astaxanthine inhibits the formation of both primary (diene conjugates) and secondary (thiobarbituric acid-reactive substances) products of lipid perioxidation. Antioxidant activity of astaxanthine is observed in the concentration range 20–100 μg/mg protein of apoB-lipoproteins. The antioxidant activity of astaxanthine is higher than that of β-carotene. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 285–288, March, 1997     

Is Na,K-ATPase the target of oxidative stress?

The susceptibility of Na,K-ATPase from bovine brain to various compounds containing active oxygen radicals is assessed. Sodium nitroprusside slightly inhibits Na,K-ATPase, while light-induced NO^o radicals (controlled by the rate of ascorbate oxidation) have no effect on the enzyme. When added in concentrations equally effective in the ascorbate oxidation assay, hydrogen peroxide and sodium hypochlorite inhibit Na,K-ATPase by 70 and 25–30%, respectively. The Fe-dinitrosyl-cysteine complex is the most potent (K_0.5=20 μM) inhibitor of Na,K-ATPase. It is demonstrated that different free oxygen radicals accumulated in the ischemic brain cause different kinds of damage to Na,K-ATPase. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 275–278, March, 1996 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Protein-bound lipids in human low density lipoproteins

In vitro oxidation of low density lipoproteins is found to be accompanied by accumulation of sterol and phospholipid residues covalently bound with apolipoprotein B. The content of protein-bound lipids in the subfraction of desialylated low density lipoproteins from healthy subjects and patients with coronary atherosclerosis is shown to be higher than that in native lipoproteins. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, No. 8, pp. 155–157, August, 1995 Presented by E. I. Chazov, Member of the Russian Academy of Medical Sciences     

Correlation between the inhibition of phosphorylation in platelet myosin light chains and the inhibition of platelet aggregation by a new calcium and calmodulin antagonist

The recently synthesized compound [1,2,5-trimethyl-4-phenyl-4-β-(N-methyl-N-4′-methoxybenzyl)-ethylamino]piperidine dihydrochloride (AR-3), which is a derivative of [1,2,5-trimethyl-4-phenyl-4-β-(N,N-disubstituted-ethylamino)]piperidines, was tested for its effects on platelet aggregation and phosphorylation of light myosin chains isolated from platelets. AR-3 caused 50% inhibition of platelet aggregation in concentrations of 25.5 to 32.2 μM (depending on the aggregation inducer used) and 50% inhibition of light myosin chain phosphorylation in a concentration of 70 μM or, when 1 μM calmodulin was added, 120 μM. The good correlation found between the inhibitory effects of AR-3 on platelet aggregation and the phosphorylation of light myosin chains from platelets indicates that this compound inhibits platelet aggregation largely by inhibiting the Ca²⁺-calmodulin-dependent phosphorylation of platelet myosin light chains, acting in this respect similarly to the well-known calmodulin antagonist W-7. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 40–42, July, 1996     

Relationship between free-radical lipid oxidation and efficiency of coronary angioplasty in coronary patients

Low-dose (250 mg daily) oral probucol produces a significant antioxidant effect in coronary patients: increases activity of glutathione peroxidase (enzyme utilizing lipoperoxides) and reduces the content of free-radical oxidation products in the blood. Probucol therapy for 7 days before and for 6 months after coronary angioplasty significantly reduces the severity of coronary artery stenosis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 503–506, November, 2007     

Mechanism of action of the new cardiotonic suphan on calcium exchange in cardiomyocytes

Effects of suphan, a new cardiotonic agent containing succinyl tryptophan, on the entry of Ca²⁺ into rat cardiomyocytes, its intracellular compartmentalization, and its exit from these cells were evaluatedin vitro. It was found that the recorded sulfan-induced rise of intracellular calcium was due to Ca²⁺ entering the cell via L-type calcium channels, and that a reversible reduction of its concentration in the sarcoplasm occurred through its accumulation in the sarcoplasmic reticulum and was blocked by the specific Ca²⁺-ATPase inhibitor thapsigargin (10 μM). Suphan did not alter the activity of Na⁺/Ca²⁺ exchange in a concentration range of 5–150 μg/ml. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 7, pp. 57–59, July, 1996     

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     

Cortisol,acth, and biosynthesis of apolipoproteins in rat hepatocytes

The effect of cortisol (5 mg/kg, 5 and 10 days) on biosynthesis of apoproteins of very low density lipoproteins in the liver and on synthesis of apoproteins of very low, low, and high density lipoproteins in blood serum of intact animals was investigatedin vivo. Cortisol, within the periods specified, inhibits biosynthesis of apoproteins of very low density lipoproteins (apo-VLDL) in liver. After adrenalectomy apo-VLDL synthesis is intensified and this effect is abolished during replacement administration, of cortisol. Apoprotein synthesis is activated 5 h after a single injection of cortisol and ACTH; a single dose and prolonged administration of cortisol give opposite results. Investigation of the specific radioactivity of apolipoproteins in the blood serum indicates a change in lipoprotein metabolism: disturbance of conversion of very low density into low density lipoproteins. An important role in the pathogenesis of the hyperlipidemia induced by cortisol within the specified period is played not by increased lipoprotein synthesis in the liver, but by a disturbance of their metabolism in the blood.All-Union Cardiological Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Prosented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 11, pp. 538–540, November, 1978.     

Effect of muscimol on the picrotoxinand bicuculline-induced delay in the desensitization of the GABA receptor/Cl− channel complex

Effects of picrotoxin and bicuculline on the muscimol-dependent³⁶Cl⁻ entry into synaptoneurosomes of the rat cerebral cortex are examined as well as desensitization of³⁶Cl⁻ entry at muscimol concentrations of 5 and 50 μM. At the 5 μM concentration (which is close to the muscimol IC₅₀), picrotoxin and bicuculline inhibited Cl⁻ entry into synaptoneurosomes and decreased the desensitization. At the 50 μM concentration, muscimol completely abolishes the bicuculline effects both on Cl⁻ entry and desensitization. Inhibition of Cl⁻ entry by picrotoxin is also abolished by 50 μM muscimol, whereas the picrotoxin-induced decrease in the desensitization rate is not. It is shown that both bicuculline effects result from inhibition of the GABA receptor, but the action of picrotoxin on the desensitization of Cl⁻ entry into synaptoneurosomes is not closely related to the functional activity of the GABA receptor/Cl⁻ channel complex. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8, pp. 144–147, August, 1996     

Effect of the phenol antioxidant katavidan on autooxidation of microsomes exposed to visible light

A study is performed of the effect of the phenol antioxidant katavidan on autooxidation of microsomes from rat liver exposed to visible light. It is shown that katavidan in a concentration of 10⁻³ M inhibits but in concentrations of 10⁻⁵–10⁻⁷ M stimulates autooxidation of microsomes. No stimulation is observed under conditions of dark incubation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, № 10, pp. 393–394, October, 1994 Presented by I. P. Ashmarin, Member of the Russian Academy of Medical Sciences     

Inhibition of platelet aggregation by monoclonal antibodies against glycoprotein IIb–IIIa complex

Monoclonal antibodies CRC64 are obtained against Ca²⁺-dependent glycoprotein IIb–IIIa complex of the platelet membrane which possess the ability to inhibit completely fibrinogen-dependent platelet aggregation. CRC64 is directed against the epitope formed by the glycoprotein IIb–IIIa complex and does not interact with proteins isolated after platelets are treated with ethylenediamine tetraacetate. Complete, reproducible blockade of platelet aggregation caused by 5 μM adenosine diphosphate is noted in an MCA concentration of 3 μg/ml, while in the case of a stronger inductor, namely 1 U/ml thrombin, platelet aggregation is inhibited in a concentration of 5 μg/ml. F(ab′)₂ fragments are also able to inhibit platelet aggregation completely and are usually effective in concentrations lower than native monoclonal antibodies. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 10, pp. 402–405, October, 1994 Presented by V. N. Smirnov, Member of the Russian Academy of Medical Sciences