Yu. V. Arkhipenko

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.

Protection of Ca++ transport by carnosine against disturbances induced by lipid peroxidation

Carnosine, an endogenous component of the muscle cell whose concentration in the myoplasm amounts to some tens of millimoles, is evidently important for muscular function. It has recently been shown that it has a stabilizing action on the system of the sarcoplasmic reticulum (SR), and also increases the working capacity of fatigued muscle [2, 6, 12]. However, the molecular mechanism of the increase in the efficiency of work of the Ca pump of the SR produced by carnosine have not been explained. We know that during exhausting physical exertion lipid peroxidation (LPO) processes in the membranous structures of the muscle cell are activated [8, 9]. It has also been recentIy shown that accumulation of LPO products in the membranes of SR results in inhibition of their Ca-transporting ability [4]. It has accordingly been suggested that the stabilizing action of carnosine may be due to its ability to inhibit LPO. The ability of carnosine to inhibit accumulation of LPO products interacting with 2-thiobarbituric acid was demonstrated previously on suspensions of mitochondria [5].

Calcium and lipid peroxidation in mitochondrial and microsomal membranes of the heart

It has recently been shown that in lesions of the heart of varied etiology (myocardial infarction, ischemia, severe stress) the key stages in the pathogenetic chain of irreversible changes in the myocardium are two simultaneously occurring processes: activation of peroxidation in phospholipids of membranous structures of the cardiomyocytes and damage to enzyme systems responsible for transmembrane transport of Ca++ [2, 3, 6].

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.

Ischemic damage to the sarcoplasmic reticulum of skeletal muscles: The role of lipid peroxidation

The development of ischemia was shown to be accompanied by inhibition of the Ca2+ enzyme transport system (ETS) (a decrease in the Ca2+/ATP ratio and in activity of Ca2+-dependent ATPase), which correlates with accumulation of the primary and secondary molecular lipid peroxidation products (POL) in vivo and in the membranes of the sarcoplasmic reticulum (SR) of the skeletal muscles. Administration of antioxidants (2,6-di-tert-butyl-4-methylphenol, α-tocopherol) prevents activation of POL in the ischemic muscle and partially protects the Ca2+ ETS against injury. Restoration of the blood flow after prolonged ischemia leads to further inhibition of the Ca2+ ETS while the concentration of POL products remains unchanged.

Effects of products of phospholipid hydrolysis by phospholipases on rhodopsin thermal stability in photoreceptor membranes

Abstract The decrease in the thermal stability of rhodopsin in sea teleost fish ( Theragra chalcogramma ) retinal rod outer segments (ROS) is strictly correlated with the increase in the amount of phospholipid hydrolysis products. The addition of exogenous unsaturated fatty acids to the ROS suspensions cause an increase of the rhodopsin thermal denaturation rate constants and a decrease of the E a value. On the other hand, saturated fatty acids at temperatures below their melting points and lysophosphatidylcholine produce practically no effect. The thermal stability of T. chalcogramma rhodopsin may be considerably enhanced when endogenous or exogenous fatty acids are eliminated by washing the ROS suspensions with a solution of fatty acid free bovine serum albumin. The role of phospholipids and their hydrolysis products in the thermal stability of rhodopsin is discussed.

Disturbances of the Ca++ transport enzyme system in membranes of the sarcoplasmic reticulum caused by hydroperoxides of phospholipids and of fatty acids

The hydroperoxide (HP) of phosphatidylethanolamine, if added to a suspension of vesicles of the sarcoplasmic reticulum (SR), was shown to have a weak activating effect on Ca-dependent ATPase and to increase the permeability of SR membranes for Ca++, measured during activity of the enzyme. HP of linoleic acid did not affect the parameters of the Ca++ transport enzyme system, the activity of Ca++-dependent ATPase, the Ca/ATP ratio, or the rate of outflow of Ca++ in SR membranes on account of the low level of its incorporation into SR fragments. It is concluded that among the primary molecular peroxidation products (HP of free fatty acids, HP of phospholipids), induced both in vitro (by the Fe+++ascorbate system) and in vivo (ischemia, avitaminosis-E), only phospholipid HP is an effective modifier of Ca++ transport in SR membranes.

Concentrations of lipid peroxidation products and antioxidant enzyme activity in myocardium and liver of rats differing in vitamin E intake

The best known natural antioxidant ~-tocopherol (TP), is not synthesized in animal cells, and accordingly the supply of this vitamin to the body depends primarily on alimentary factors [13]. It has been shown that vitamin E deficiency causes the development of certain functional and structural disturbances of the motor apparatus, the regenerative system, the myocardium, and so on [i, ii, 13]. It has been shown to be possible, in principle, to modify activity of antioxidative enzymes by administering TP [6]. Nevertheless, data in the literature on changes in activity of the protective enzymes following variation of the vitamin E level in the tissues are contradictory and, moreover, the investigations themselves are insufficiently systematic.

Accumulation of lipid peroxidation products in the lens in cataract

The development of senile cataract is accompanied by disintegration of the membranous structures of the lens [8]. Among endogenous processes which can cause injury to membranous structures of cells and tissues one of the most important is lipid peroxidation (LPO). During aging and, in particular, during the development of senile cataract, activity of enzymic (superoxide dismutase, glutathione peroxidase, catalase) and nonenzymic (ascorbate, cysteine, glutathione) antioxidant systems in the lens and aqueous humor is reduced [6, ll, 14]. Accumulation of LPO products in the lens may he facilitated by the presence of compounds in the lens which are photosensitizers of free-radical oxidation reactions of the 3-hydroxykynurenin or N-formylkynurenin type, which absorb light in the near UV-region of the spectrum (360-400 nm). These photo-oxidation products of tryptophan, under the influence of light, can generate active forms of oxygen and products of its successive single-electron reduction (singlet oxygen, superoxide anion-radicals, hydrogen peroxide, hydroxyl radicals), which can be found in the lens tissue and also in the aqueous humor [13].

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