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Results of studies of lipid inhibitors of phospholipase A2 are reviewed with a special emphasis on substrate specificity, special features of interfacial catalysis, and methods for the determination of the enzyme activity. The biological function of intracellular phospholipases is considered, and the possible use of inhibitors of a lipid nature for the modulation of the enzyme activity in pathological states of the human organism is discussed.

Multilamellar phosphatidylcholine liposomes have been shown to possess antibacterial activity with respect to Pseudomonas aeruginosa and Staphylococcus aureus. An increase in the level of lipid peroxidation products in liposomal suspension as the consequence of the earlier oxidation of liposomal lipid leads to a considerable increase in the antibacterial activity of liposomes. The pH of the liposomal suspension has also an essential influence on its activity. If the pH of the suspension has acidic values, its antibacterial activity increases. The bactericidal action of liposomal suspension is more pronounced with respect to S. aureus, than to P. aeruginosa.

Effect of 6-methyluracyl (MU) on oxidative processes was studied on model systems of different degrees of complexity (methyloleate model, mitochondria isolated from rat liver, surviving slices of mammalian muscle tissues). On two former models it was shown that MU exerted antioxidant (AO) properties inferior to those of such antioxidants as ionol and K(+)-phenosan. The AO efficiency depended on the intensity of peroxide processes. The AO activity of MU was most fully realized on the model of isolated surviving slices of muscle tissue. The totality of data obtained suggests that participation of the substance in regulation of lipid peroxidation in the organism underlies its therapeutic activity in pathological states.

The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti-ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation. The conclusion is drawn that there is a possibility of using ionol in doses of 10(-6) to 10(-5) M as a constituent of liposomes for addition to perfusion, conservant and cardioplegic solutions as an anti-ischemic remedy.

In experiments on 34 dogs, the authors studied myocardial rigidity, ATP levels and Ca2+-accumulating function of the membranes of the sarcoplasmic reticulum (SR) in the external (subepicardial) and internal (subendocardial) layers of the myocardium at 1 and 2 h of total ischemia at 37 degrees C and also 30 min after cardiac reperfusion by heterotopic transplantation. It was revealed that contracture changes in ischemia first affect the internal and then the external layer of the myocardium which corresponds to the initial and completed phases of ischemic contracture (IC) of the heart, correspondingly. IC of the heart is irreversible and in cases of total contracture of all layers of the myocardium (the completed phase) the heart loses contractile function. Changes in the contractility in the external and internal layers of the myocardium show a stronger inverse correlation with the capacity of SR membranes to absorb Ca2+ rather than with ATP levels in the tissues which indicates an essential role of the Ca2+ accumulating function of SR in the pathogenesis of IC.

The study on the possibility of eliminating gramicidin S from the bacterial cells which had adsorbed it showed that a part of the labeled antibiotic bound by the bacteria may be washed out with buffer or salines. When the cells which had adsorbed gramicidin S were treated with lecithin emulsion, a significant part of the bound antibiotic was transferred to the lecithin liposomes. This turned the gramicidin S effect to the cells: significant but not complete reduction of the membrane barrier properties and dehydrogenase reactivation. Elimination of gramicidin S also reduced the colony forming capacity in a part of the cells.

In experiments on perfused isolated Wistar rat hearts and frog myocardial strips it has been shown that the injection of egg phospholipid liposomes in the perfusion solution leads to a decrease in the volume velocity of the coronary perfusion and to worsening of the contractile myocardial function. Negative inotropic effect of phospholipids on the perfused heart may be linked not only with the decrease in the coronary perfusion but also with their direct inhibitory action on the contractile ability of myocardiocytes.

In 30 experiments on mongrel dog hearts it was shown that 30 min of total ischemia (37 degrees C) followed by accumulation of MDA in the SR membranes and decrease of their Ca2+-uptake, but had no effect on activity Ca2+-ATPase. After 60-120 min ischemia marked a decrease of Ca2+-uptake and activity Ca2+-ATPase took place, MDA content remained at the increased level. The results show that lipid peroxidation take part in the increase of the permeability of SR membranes for Ca2+ and inhibiting of Ca2+-ATPase.

It has been shown that introduction of the fraction of phosphatydylethanolamine enriched with primary products of peroxidation-hydroperoxides-into bilayer lipid membrane (BLM) results in the rise of permeability of BLM towards H+ and K+ ions. The effect depends on the background permeability of the membrane and on the introduction method of the fraction enriched with hydroperoxides (FEHP) into monolayer or into both layers of BLM. Absence of the effect while including hydroperoxides into the membrane monolayer with low background conductivity and growth of BLM conductivity when introducing FEHP into both monolayers of the membrane permits a substantiation of the "Cluster" mechanisms of the membrane permeability increase with the accumulation of phospholipid hydroperoxides.

Experiments were made on Wistar rats with 6h tourniqueting of the hind limbs to study animal survival rate, myocardial contractile function and protective action of antioxidants and egg phospholipid liposomes during ischemic shock. It has been shown that reperfusion of the limbs leads to a high animal lethality, make lower myocardial contractile function and coronary flow of the hearts isolated from rats following a 6h reperfusion of the limbs. Well-known antioxidant butylated hydroxytoluene and a new antioxidant tetramethylpiperidine derivative bring animal lethality down and improve coronary flow and contractile function of the isolated heart. Phospholipid liposomes increase survival rate moderately but have no any effect on the heart contractile function. It has been deduced that lipid peroxidation takes part in the disturbance of heart contractile function and genesis of the death within ischemic shock.

Effects of oxidized yolk phospholipids (PL) on the coronary perfusion rate (CPR) and myocardial contractility were studied in the experiments with the isolated or isolated and 30-minute ischemia-induced heart of the rat or isolated myocardial strip of the frog. The oxidized PL were demonstrated to possess a more pronounced and steady negative inotropic effect than unoxidized PL, which was due to their direct dose-dependent damaging action on myocardial contractility. The oxidized PL also made the unrestored CPR worse in the early postischemic period, the concomitant administration of aspirin producing no effects and that of the antioxidant ionol making ischemic myocardial contractility better. The findings suggest that the circulating oxidized PL may contribute to the impairment of coronary tone and contractility of the intact or ischemic myocardium and the induction of endogenous processes of lipid peroxidation plays a role in showing these effects.