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The increased generation of reactive oxygen species (ROS) by mitochondria under stress conditions leads to lipid peroxidation (LPO) as a consequence of the ROS interactions with polyunsaturated fatty acids in the lipid bilayer of cell membranes, causing their damage. It was assumed that chemical preparations that reduce the excessive ROS generation by mitochondria should exhibit protecting properties under oxidative-stress conditions. In this context, the antioxidants resveratrol (RSV) and 2-ethyl-6-methyl-3-hydroxypyridine N-acetylcysteinate (NAC-3-HP) were examined as potential chemical protectors upon the exposure to stress, able to maintain the functional state of mitochondria.

It was established that the administration of an aqueous solution of bis(µ-tartrato)di(μ-hydroxy) germanate (IV) triethanolammonium to animals daily for 2 months at a dose of the active substance of 10 mg/kg of the animal's weight leads to inhibition of the total activity of the alkaline phospholipase A 2 of mononuclear cells. The results of the study can be used to correct lipid metabolism in the development of disorders in hyperlipidemia. This makes it possible to expand the scope of use of the studied substance and create new pharmaceuticals based on bis(µ-tartrato)di(μ-hydroxy) germanate (IV) triethanolammonium prevent and inhibit the development of hyperlipidemia.

Energy status of rats was altered after administration of anphen [2,4-(hydroxy-3,5-ditretbutyl phenyl)-2-aminomalonic acid] at a dose of 40 mg/kg. Within 30 min after administration, maximal rates of NAD-dependent substrates and succinate oxidation were detected in liver mitochondria, which appears to occur due to activation of the mitochondrogenesis. The rate of electron transport in respiratory chain of mitochondria was decreased 1.3-1.6-fold within 1-1.5 hr, whereas within 3 hrs the patterns of oxidation and energetic coupling in liver mitochondria were reduced to control values. The similar alterations were observed in activities of lymphocyte alpha-glycerophosphate- and succinate dehydrogenases. Shifts in the pool of lipid peroxidation products in biological membranes was apparently responsible for alterations in activity of the energy metabolizing enzymes in lymphocytes and liver mitochondria.

Experiments were carried out to investigate effects of heavy metal salts and phenol both alone and in different combinations on respiration rate and coupling of respiration and oxidative phosphorylation by rat liver mitochondria. Oxygen consumption measurements were obtained using a Clark electrode and lactate plus glutamate as substrates. It is shown that a 50% decrease of the respiratory rate was achieved in less concentrations of substances in the mixture compared with the effects of the individual substances. For respiratory control recovery by EDTA titration more amounts of complexion for model mixtures was necessary. The results evidence synergism of the substances responsible for a considerable increase in toxicity. Mitochondrial test-systems are suggested for rapid prognosis of toxicity of multicomponent mixtures of substances.

The effect of toxic substances on the functional state of liver mitochondria has been studied. It has been shown, that the contact of toxic substances with mitochondria lead to the reduction of the degree of association of oxidation with phosphorylation. EDTA in concentrations necessary to inhibit lipid peroxide oxidation prevents toxic effects. Preliminary antioxidant treatment of mitochondria prevents toxic damage of membranes. A close correlation has been established between chemical compounds toxicity and the concentration of antioxidants necessary for the prevention of toxic effects, as well as between chemical compounds toxicity and cumulation of malonic dialdehyde in mitochondria membranes.

Concentration of cytochroms in the liver of adult male rats has been studied during the acclimation to cold. One group of rats was kept at about 24 degrees, another at 2--4 degrees. After a month of acclimation to cold the cytochroms concentration in the liver increased, whereas the mitochondrial concentration of cytochroms remained unchanged. It is possible to distinguish three steps of cytochroms concentration changes; 1. on the 9th day of acclimation to cold cytochroms concentration increased 1.5--2 times; 2. by the 14th day the cytochroms concentration decreased (to the control level and lower); 3. after about one month of acclimation to cold the cytochroms concentration increased again. In the skeletal muscle it increased on the 14th (but not on the 9th) day.

Injections of albino rats with antioxidants of the ionol group cause cyclic changes in the energy state of liver mitochondria which are correlated with changes in the fatty acid composition of mitochondrial membranes. The increase in the degree of coupling between oxidation and phosphorylation coincides in time with the increment in the content of saturated fatty acids and a decrease in the unsaturated fatty acid content in the total fraction of mitochondrial membrane lipids. Conversely, the activation of the external pathway of NADH oxidation and a decrease of the respiratory control are correlated with the diminution of the saturated fatty acid content and an increased percentage of unsaturated fatty acids. These changes are especially well pronounced in the case of fatty acids carrying 18 carbon atoms.

Activation of the external pathway (amytalantimycine A-resistant) of the exogenous NADH oxidation was studied in rat liver mitochondria after long-term (within 6 days) administration of pyracetame. Stimulation of lipid peroxidation and a decrease in viscosity of mitochondrial membranes accompanied the increase in the rate of oxygen consumption in mitochondria in presence of the exogenous NADH, amytal and antimycine A.

15 min cold exposure of rats adapted to cold results in switching on a pathway of the fast oxidation of extramitochondrial NADH in the isolated liver mitochondria. This pathway is sensitive to mersalyl and cyanide, resistant to amytal and antimycin A, and can be stimulated by dinitrophenol. A portion of the endogenous cytochrome c pool can easily be removed by washing mitochondria of the cold-exposed rats. A scheme is discussed, postulating desorption of the inner membrane-bound cytochrome c into intermembrane space of mitochondria, resulting in formation of a link between the non-phosphorylating NADH-cytochrome c reductase in the outer mitochondrial membrane and cytochrome c oxidase in the inner membrane. It is suggested that such an oxidative pathway is involved in the urgent heat production in liver in response to the cold treatment.

An injection of ionol-type antioxidants stimulates fast oxidation of extramitochondrial NADH in isolated liver mitochondria via an external pathway, which is sensitive to cyanide and resistant to amital and antimycin A. This activation is accompanied by a decrease in cytochrome a and cytochrome (c + C1) levels in liver homogenate. Part of the cytochrome c pool can be removed by washing the antioxidant-treated mitochondria. It is assumed that the injection of the antioxidants leads to desorption of the cytochrome c bound to the inner membrane into the intermembrane space of mitochondria. This cytochrome acts as a linking agent between NADH cytochrome c reductase of the outer mitochondrial membrane and cytochrome c oxidase of the inner membrane. The Li-derivative of ionol (5 x 10(-4) and 10(-3) M) decreases the transmembrane potential of the submitochondrial particles from bovine heart by 15-20%.