[Vitamin A and enzyme systems of metabolic activation of genotoxic compounds]. / Vitamin A i fermentnye sistemy metabolicheskoi aktivatsii genotoksichnykh soedinenii.

The study was undertaken to study the effects of N-nitrosodimethylamine (NDMA) on the formation of single-strand DNA breaks and gamma-glutamyltransferase-positive knots, the status of the enzymatic systems involved in NDMA metabolism and some other biochemical parameters when rats were on retinol-deficient diets and when they were given excessive vitamin A. The action of retinol on NDMA effects were analyzed by evaluating the activity of glutathione-S-transferase (EC 2.5.1.18), glutathione-reductase (EC 1.2.1.1), aldehyde-dehydrogenase and aldehyde-oxidase (EC 1.2.1.3 and EC 1.2.3.1, respectively), p-450 reductase NADPH cytochrome (EC 1.6.2.4), the demethylase and hydroxylase activities, levels of malonic dialdehyde and the rate of ascorbate-dependent lipid peroxidation, the contents of proteins, phospholipids, cysteine, redox glutathione, glucuronides, sulfates. The level of vitamin A in the animals was found to substantially affect the magnitude of the genotoxic action of NDMA. The supplementary administration of vitamin A reduced the effect of the carcinogen. The mechanism of protective action of retinol was largely explained by the mediated activity of cytochrome-P-450 and glutathione-dependent systems involved in the biotransformation of NDMA. Based on the data available in the literature and their own data, the authors analyzed the effects of retinol on the metabolism of genotoxicants and described possible mechanisms of its antimutagenic and anticarcinogenic action. It is concluded that the effective protection of the body from unfavourable environmental influences may be provided only by supplementary (more than the optimum) intake of vitamin A against the background of a damaging factor.

[Biotransformation and toxicity of xenobiotics in various routes of administration of vitamin A into the rat body]. / Biotransformatsiia i toksichnost' ksenobiotikov pri razlichnom postuplenii vitamina A v organizm krys.

Deficiency of vitamin A in rats caused a decrease in metabolic rate of acetanilide as well as in elimination of voltaren from blood plasma, while excess of the vitamin (3,000 IU/kg) stimulated voltaren elimination and increased excretion with urine of aminophenol conjugates of acetanilide with sulfuric and glucuronic acids. Under conditions of vitamin A deficiency formation of acetanilide toxic metabolites was increased as a result of which excretion of mercapturic acids with urine was elevated but excess of vitamin A and its hyperdose inhibited these reactions. At the same time, deficiency of vitamin A amplified the paracetamol and voltaren toxicity and its excess exhibited protective effects.

[Body vitamin A allowance of rats as a factor affecting the metabolism and toxicity of xenobiotics]. / Obespechennost' organizma krys vitaminom A kak faktor, vliiaiushchii na metabolizm i toksichnost' ksenobiotikov.

In experiments on albino rats it was shown that vitamin A deficiency delays and its excess enhances biotransformation of aminopyrine and benzoic acid. Vitamin A excess exerted the protective effect in acute intoxication with bromobenzene, cyclophosphamide and dimethylnitrosamine.

[Effect of vitamin A deficiency on surfactants and enzymes of xenobiotic metabolism in the rat lung]. / Vliianie defitsita vitamina A na surfaktanty i fermenty metabolizma ksenobiotikov v legkikh u krys.

Experiments were conducted on 128 male rats kept on a retinol-deprived diet during 12-14 weeks, that resulted in vitamin A deficiency. The content of phospholipids, total lipids, proteins and the activity of esterase, glutamate dehydrogenase, catalase, glutathione-S-transferase, aldehyde dehydrogenase and aldehyde oxidase were assayed in the bronchoalveolar lavage fluid, in homogenates and microsomes of the lungs. The content of phospholipids in the bronchoalveolar lavage fluid was reduced up to 63.9%, as compared to that in the control rats, while the protein content was unchanged. The levels of phospholipids, total lipids and protein rose in the homogenates and microsomes of the lungs. Esterase activity decreased up to 38.6% of the control level, catalase--up to 73.2%, glutamate dehydrogenase--up to 79%. There was a tendency to decrease in glutathione-S-transferase activity, while aldehyde dehydrogenase and aldehyde oxidase activities remained unchanged. It is suggested that the disorders in the enzymatic activity and lipid content in the surfactant can be responsible for the changes in the xenobiotic biotransformation and for the rise in xenobiotic toxicity.

[Vitamin A and E allowance of the body in xenobiotic exposure]. / Obespechennost' organizma vitaminami A i E pri deistvii ksenobiotikov.

The results are presented of the clinico-experimental studies conducted in patients with diseases of the respiratory organs. Providing with tocopherol, lipid metabolism and peroxidation parameters were studied in these patients in the time course of combined drug therapy. Different variants of providing with vitamins A and E were simulated in rats. It was shown that both under clinical and experimental conditions, administration of xenobiotics produced the devitaminizing effect which was manifest in tocopherol and retinol deficiency, activation of lipid peroxidation in the blood, bronchoalveolar lavage, in the lungs and liver. The authors have recommended the control over providing with vitamins A and E during the drug therapy of such patients, as well as differential approach to the corrective dietotherapy with the rations enriched with vitamins A and E; the vitamins are especially necessary for the patients with chronic broncho-pulmonary diseases in the presence of obesity and lipid metabolism disorders.

[Carbohydrates in the liver microsome fraction of rats with hypovitaminosis A]. / Uglevody vo fraktsii mikrosom pecheni krys s A-gipovitaminozom.

Accessibility for trypsin and sodium deoxycholate was determined in carbohydrates of glycoproteins in the liver microsome fraction of rats, which were kept for 80 days on retinol-deficient diet and received optimal amounts of vitamin A. It was found that the prevailing amount of hexose- and glucosamine-containing glycoproteins is located on the outer surface of membrane vesicles and only a smaller part of these proteins is submerged into the lipid layer of the membrane or is located on its inner surface. Above a half of protein bound with fucose and neuraminic acid is located in the lipid layer. Retinol deficiency leads to translocation of a portion of fucose- and hexose-containing proteins on the outer surface of vesicles and to a decrease of the share of these proteins in the hydrophobic membrane zone.

[Effect of retinol deficiency on the activity and solubility of various enzymes of the endoplasmic reticulum membranes in the rat liver]. / Vliianie defitsita retinola na aktivnost' i soliubilizatsiiu nekotorykh fermentov membran éndoplazmaticheskogo retikuluma pecheni krys.

Solubilization by sodium deoxycholate and trypsin of some metabolic enzymes of unrelated compounds associated with endoplasmic reticulum membranes was carried out. The effects of urea, butanol and detergents on the retinol content in the membranes were studied. It was shown that retinol deficiency causes changes in the interactions of NADH-arylesterase with microsomal membrane components that are manifested in the decrease of the activating effect of butanol and low detergent concentrations on the NADH-reductase activity as well as in the increase in the damaging effect of urea and high detergent concentrations on the enzyme activity. Under conditions of retinol deficiency, the degree of solubilization of NADH-reductase, hydroxylase and arylesterase in the presence of sodium deoxycholate is enhanced. After treatment of liver microsomes of retinol-deficient animals with trypsin or with a trypsin-sodium cholate mixture, the content of these enzymes in the supernatant becomes much greater than that in liver microsomes of vitamin A-deficient rats. It is assumed that retinol deficiency causes of weakening of hydrophobic interactions within the membrane as well as partial translocation of the enzymes from the hydrophobic to the hydrophilic layer.