Sazontova Tg

The role of lipid peroxidation in pathogenesis of arrhythmias and prevention of cardiac fibrillation with antioxidants

SummaryThe present paper shows the arrhythmogenic effect of a direct induction of lipid peroxidation (LP) on isolated auricles; it is demonstrated that preendured stress potentiates this effect, while antioxidants prevent it. Subsequently, in studying the mechanism of the LP arrhythmogenic effect it was established that stress, like the LP induction, disorders the activity of Na, K-ATPase and accelerates thermodenaturation of this enzyme which plays a key role in maintaining the transmembrane potential and the electrical stability of the heart. Antioxidants prevent the enumerated shifts. Based on these data, the antioxidant BHT was successfully applied for prevention of the fall in cardiac fibrillation threshold in stress and experimental myocardial infarction, and also for prevention of cardiac fibrillation itself under acute ischemia and reoxygenation of the heart.

Kinetic approach for evaluation of total antioxidant activity

We propose a novel approach for assessment of total antioxidant activity by monitoring kinetics of hydrogen peroxide (H(2)O(2)) scavenging after its injection into liquid sample under study. H(2)O(2) is known to be the strongest oxidant, really presented in human body in contrast to the majority of the model oxidative systems used for evaluation of antioxidant activity. In addition, kinetic approach, being more informative than the commonly used determination of the final product, obviously provides better discrimination of potential antioxidants. Prussian Blue based sensor due to its high sensitivity and operational stability allowed to monitor kinetics of hydrogen peroxide consumption in turbid and colored samples. The pseudo-first order kinetic constants of hydrogen peroxide scavenging in the presence of different food additives correlated with total antioxidant activity of these samples evaluated via standard procedure based on lipid peroxidation. However, in contrast to the standard method, the proposed kinetic approach is expressed and does not require fresh biological tissues.

Mechanisms of the cardioprotective effect of a diet enriched with ω-3 polyunsaturated fatty acids

Abstract The review presents current views of metabolic conversions of class ω-3 polyunsaturated fatty acids (ω-3 PUFA) and their effects on the heart function. The role of these compounds in regulation of the membrane lipid composition is discussed. Within the organism, ω-3 PUFA incorporate more effectively into membrane phospholipids of the myocardium in comparison with other organs. In animals kept on a ω-3 PUFA-enriched diet, the intramembrane concentration of ω-6 PUFA, in the first place, of arachidonic acid, decreases. Substitution of ω-3 PUFA for arachidonic acid in the metabolic system of eicosanoid synthesis initiates the synthesis of prostaglandins and thromboxanes possessing lowered biological activity, thus minimizing the risk of clot formation in the cardiovascular system. As ω-3 PUFA are direct substrates for lipid peroxidation, any rise in ω-3 PUFA concentration sharply activates free-radical oxidation in the membranes of internal organs particularly in the liver. Original data are presented that in rats kept on ω-3 PUFA-enriched diets, the kinetic parameters of the Ca 2+ transport system do not change. However, the resistance of the system to free radical oxidation increases considerably. This may increase myocardial resistance to free-radical-dependent injuries. A rise in the intramembrane ω-3 PUFA content which brings about structural rearrangements within lipids and changes the activity of membrane-bound enzymes in vitro, has no effect in vivo. This finding points to the existence of a mechanism compensating for changes in the fatty acid composition of foods. Data from literature analysis suggest that one of the most active participants in the compensatory system is α-tocopherol, a lipid peroxidation inhibitor and a structural stabilizer of biomembranes. With a rise in ω-3 PUFA concentration, α-tocopherol is released from the liver and blood flow and accumulated in the body (predominantly in myocardial membranes). Whereas potent chemical antioxidants display an ability to inhibit physiologically important free-radical reactions occurring in the organism, vitamin E is without side effects even when used at high concentrations. In case of long-term application of ω-3 PUFA-enriched diets, α-tocopherol must be added to the diet.

Adaptation to periodic hypoxia and hyperoxia improves resistance of membrane structures in heart, liver, and brain.

A novel principle of short-term periodic adaptive training by varying the oxygen level from hypo- to hyperoxia is substantiated both theoretically and experimentally. Short-term adaptation to hypoxia-normoxia produced a membrane-protective effect in the heart and cerebral cortex, but increased the sensitivity to free radical oxidation and decreased the level of components of the antioxidant defense system in the liver. Hypo-hyperoxia adaptation produced a membrane-stabilizing effect in the heart, brain, and liver, which was more pronounced compared to the effect of hypoxia-normoxia training. In contrast to hypoxia-normoxia adaptation, in case of hypo-hyperoxia training the adaptive defense developed as early as 15 days after the start of training.

Ca2+ transport by rat skeletal muscle sarcoplasmic reticulum during load relief of the hind paws

A weightless state involves bone tissue demineralization, skeletal musculature atrophy, and hemodynamic changes. Ground-based experiments simulating physiological effects of weightlessness (restricted mobility in narrow cases, suspending rats to relieve weight on the hind paws) lead to changes similar to those observed under microgravitation conditions [3-5,10,13]. Suspending animals by the tail is also known to cause significant changes in histochemical, enzymatic, and contractile characteristics of the muscles [6]. The status of the muscle tissue Catransporting system under conditions of weightlessness and hypokinesia hypodynamia is still little known. The characteristics of the sarcoplasmic reticulum membranes have been shown to change markedly for dystrophic processes in the muscle [18,19]. Moreover, a study of Ca 2§ transport in sarcoplasmic reticulum of rat m. so&us classified as the slow type has revealed that suspending an animal is associated with increased Ca 2§ accumulation and release, as well as with an increase of passive calcium release in caffeine-induced contracture [17]. The present study was aimed at, f~rst, elucidation of the effect of rat hind paw off-loading

Activation of rat brain Na,K-ATPase by stress

: The clonal and tissue-specific character of the heterogeneity of diploid fibroblasts obtained from different tissues of human embryo has been demonstrated. It has been discovered that the cells differ in the intensity of proliferation, morphology, and alkaline phosphatase activity.

Addition of Hyperoxic Component to Adaptation to Hypoxia Prevents Impairments Induced by Low Doses of Toxicants (Free Radical Oxidation and Proteins of HSP Family)

We studied the possibility of preventing disturbances caused by administration of low doses of toxicants by adaptation to interval hypoxia and hyperoxia. The preventive protective effect of adaptation to hypoxia–hyperoxia manifested in suppression of free radical oxidation, decrease in the levels of HIF-1α and inducible HOx-1, and improvement of tolerance to physical exercises.

Adaptation to Intermittent Hypoxia/Hyperoxia Enhances Efficiency of Exercise Training

This chapter provides an overview of the current concepts on redox signaling pathways, particularly, under hypoxic conditions. The principle of intermittent adaptation effects of variable oxygen levels (short-term hypoxia and hyperoxia) was substantiated and confirmed experimentally in vivo for the first time. The goal of our experiments in rats was to estimate (1) efficiency of physical training conducted separately and in combination with adaptation to intermittent hypoxia/hyperoxia, (2) changes in the rates of free radical processes, and (3) concentration of heat shock proteins (HSP). We found that short-term physical training increased the duration of swimming in acute exhaustive exercise. Combination of physical training with adaptation to hypoxia–normoxia had no effect on this parameter, while adaptation to physical load combined with adaptation to hypoxia–hyperoxia increased the duration of the active swimming phase and, as a consequence, the efficiency of adaptation. Adaptation to physical load and its combination with adaptation to variable oxygen levels increased the resistance of membrane structures to free radical oxidation at the expense of excessive activation of antioxidant defense enzymes in the course of physical training, which was partly compensated for by adaptation to hypoxia/normoxia and was fully prevented by adaptation to hypoxia/hyperoxia. Combination of two forms of adaptation to physical load and to variable oxygen levels markedly compensated/reversed the elevated content of HSP in the course of physical training, which is especially well pronounced during adaptation to hypoxia/hyperoxia. The novel technique is biologically less expensive and more beneficial for the organism.

Opposite effects of adaptation to continuous and intermittent hypoxia on antioxidative enzymes

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Role of lipid peroxidation in inhibition of cardiac Na,K-ATP-ase during stress

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