[Effect of the interaction of formaldehyde and nitric oxide metabolism pathways in mechanism of their toxic action. I. Exo- and endogenous sources of formaldehyde and nitric oxide. Toxic action of formaldehyde].

Possible exogenous sources of formaldehyde and nitric oxide have been considered; the environment pollution conditions under which these compounds and their precursors have mutual effect on the organism; endogenous sources of FA and NO which are intermediates of the metabolism and key enzymes of their transformation (semicarbazide-sensitive amine oxidase and NO-synthase) the role of the C1 metabolic cycle pathways and methyl cycles in the FA formation and accumulation have been considered as well, various paths of FA toxic action have been characterized.

[Role of metabolism pathway interaction of formaldehyde and nitric oxide in the mechanism of their toxic effect. 2. Toxic effect of nitric oxide].

Toxic properties of NO in organism are realized under its hyperproduction and inhibition of the system of anti-oxidant protection as a result of complex chemical transformations, the transient metals, oxygen, superoxide and other radicals being their main participant. Here direct paths (through formation of nitrosil complexes with the gem and nongem iron) of the toxic action of NO and the path mediated by active forms of nitrogen are found, which disturb various biomolecules and subcellular component through the reactions of S- and N-nitrozation, nitration, oxidation, desamination and other reaction, cause metabolic disbalance and death of cells by the type of apoptosis or necrosis. A possible mechanism of the death of cells caused by NO was considered on the example of thymocytes. According to this mechanism one of early stages of this death is a decrease of the cell fund of AP, intensification of catabolism of adenine nucleotides and transformation of xanthine oxidoreductase from D-form (xanthine dehydrogenase) of O-forms (xantine oxidase) which catalizes formation of cytotoxic molecules of superoxide and hydroperoxide. This cytotoxic mechanism which includes transformation of xanthine oxidase system, is probably, universal and does not depend essentially on the starting factor.

[Metabolism of adenine nucleotides in thymocyte cytoplasm and subcellular fractions after treatment with concanavalin A, papaverine and adenosine]. / Metabolizm adeninnukleotidov v tsitoplazme i subkletochnykh komponentakh timotsitov pri deistvii konkanavalina A, papaverina i adenozina.

Studies with rat thymocytes labeled with [14C]adenine and fractionated by digitonin treatment revealed that the cytoplasm of these cells contains about 60% of the total adenine nucleotide pool with a higher ATP/ADP ratio and metabolic activity as compared with the structural components. The incorporation of [14C]adenine and [14C]adenosine into thymocyte adenine nucleotides results in predominant labeling of cytoplasmic ATP, in which the specific radioactivity of this nucleoside triphosphate is two and three times as high as in subcellular structures. Concanavalin A decreases the ATP level in thymocytes without changing its specific radioactivity. This compound does not influence the total content and amount labeled adenine nucleotides in the structural fraction. Papaverine accelerates the catabolism of ATP, mainly in thymocyte cytoplasm and, in a lesser degree, in its structural fraction. In each fraction the papaverine-induced catabolism of ATP is localized in the compartment which is more intensively labeled with [14C]adenine than the whole fractionation ATP pool. Adenosine markedly accelerates adenine nucleotide catabolism in the cytoplasmic and structural fractions of thymocytes; however, only in the first one of them this acceleration is due to ATP elevation. Papaverine and adenosine do not directly influence either the content or specific radioactivity of adenine nucleotides of the structural fraction isolated from [14C]adenine-labeled thymocytes.

[Combined effect of adenosine and papaverine on the metabolism of adenine nucleotides in rat thymocytes]. / O sovmestnom deistvii adenozina i papaverina na metabolizm adeninnukleotidov v timotsitakh krysy.

It is shown that in [14C]adenine-labelled thymocytes adenosine increases the content of adenine nucleotides and simultaneously accelerates their catabolism. Papaverine induces acceleration of splitting and a decrease of the specific ATP radioactivity but increases the AMP content and its specific radioactivity. The both effectors intensify considerably the outlet of total radioactive label from cells. If the papaverine effect in the extracellular medium results in accumulation mainly of hypoxanthine in the extracellular medium then the adenosine presence causes accumulation of inosine and hypoxanthine approximately in equal amounts. The release of labelled adenosine from thymocytes in all cases is an insignificant part of extracellular radioactivity. A conclusion is drawn that under conditions of the combined action of the substances under study papaverine removes the adenosine effect caused by its under study papaverine removes the adenosine effect caused by its phosphorylation with the formation of ATP and exerts the dose-depended action on adenine nucleotide metabolism in thymocytes.

[Effect of adenosine and adenine nucleotides on rat thymocyte blast transformation induced by concanavalin A]. / Izuchenie vliianiia adenozina i adeninnukleotidov na blasttransformatsiiu timotsitov krysy, vyzvannuiu konkanavalinom A.

Studies on the action of adenine nucleotides on the Con A-induced blast transformation of rat thymocytes have shown that addition of milimolar concentrations of AMP and ADP to the cultural medium as well as that of adenosine produce an inhibitory effect on the reaction. Addition to the cells of adenosine deaminase almost completely abolishes this effect. Unlike the nucleotides, the suppressant effect of ATP on thymocyte proliferation is less pronounced and is not reversed by addition of adenosine deaminase. cAMP and ATP given in the concentrations sufficient for giving rise to the protein kinase reaction and ammonium ions (1 mM) have no effect on thymocyte blast transformation. The latter is appreciably suppressed by 1 mM pyrophosphate and almost completely by papaverine and curantyl. The nucleotides added to the thymocytes get dephosphorylated, however, extracellular adenosine is not accumulated during 80 minutes, its concentration being of the order of 10(-6) M.