[Effect of beta-carotene on nuclear lipids in the rat liver in normal conditions and after low-dose gamma-irradiation].
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Biomedical subjects
Publications and source records attributed to A M Kuzin.
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Chronic gamma irradiation of rats at a dose rate of 12.9 rad/day for 155 days (total dose 20 Gy) did not change the cholesterol level in the brush border membrane of the small intestine. Maintenance of rats on a beta-carotene-enriched diet (daily throughout the irradiation period, at a diurnal dose of 3 mg/kg body weight produced an increase in cholesterol levels in the small intestinal brush border membranes. The phospholipid level after gamma irradiation alone did not change, but it was increased in gamma-irradiated rats fed with carotene, this increase being most pronounced for sphingomyelin. Beta-carotene decreased the cholesterol/phospholipid ratio in the brush border membrane of irradiated rats. Activation of lipid synthesis (as seen from inclusion of 2-14C-acetate in the epitheliocyte lipids of irradiated animals) and no influence of beta-carotene on the inclusion of the label in small intestine epitheliocytes of irradiated animals have been revealed. In the presynaptic membranes of brain nerve endings, chronic gamma irradiation of animals produced a deep fall of cholesterol and phospholipid levels. Also, a tendency was revealed for stimulation of transport of the neurotransmitter amino acids GABA and L-glutamate across the presynaptic membranes of nerve endings. Beta-carotene normalized the phospholipid and cholesterol levels in brain presynaptic membranes of irradiated rats, as well as decreased L-glutamate transport. It is assumed that the modifying and normalizing effects of beta-carotene on the lipid exchange of plasma membranes upon chronic irradiation of animals and permanent introduction of the drug are associated with the radioprotector activity of beta-carotene.
The influence of continuous gamma irradiation on the lipids of nuclei and chromatin of rat liver at a dose-rate of 0,129 Gy/day for 155 days (a total dose of 20 Gy) and by feeding of ubiquinone-9 has been studied. The amount of phosphatidylcholine with phosphatidylserine and phosphatidyl-ethanolamine in liver nuclei of irradiated rats was found to increase. Ubiquinone-9 had a normalizing effect. A decrease of cardiolipin was observed in the liver chromatin of irradiated rats. The amount of free fatty acids had a tendency to decrease in homogenate, nuclei and liver chromatin of irradiated rats. Ubiquinone was found to increase the amount of free fatty acids up to the control level. The amount of cholesterol in nuclei was increased after irradiation and that in chromatin tended to rise. Ubiquinone-9 significantly decreased the amount of cholesterol in nuclei and chromatin of irradiated rats.
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The response of the receptor of plant origin, phytochrome and the receptor of rat lung cytoplasmic membrane adenylate cyclase to chronic, growth- and development-stimulating low-dose gamma-radiation (0.36 and 0.036 cGy/day) has been studied. The influence of radiation results in sensitization of receptors to specific effectors and receptor-mediated stimulation of corresponding enzymes.
The ability of polypeptides consisted of aspartic and glutamic acids to inhibit the repair and to promote the formation of unrepaired double-strand DNA breaks and chromosomal aberrations in gamma-ray induced Chinese hamster cells was shown. A complete inhibition of the double-strand DNA breaks repair was observed at the concentrations of 20 mu M/l (polyglutamic acid with molecular weight 2000-15,000 daltons) and 100 mu M/l (aspartylglutamic acid with molecular weight 1500-4500 daltons). Both polypeptides were low toxic at the given concentrations.
The effect of chronic radiation, 100, 1000 and 4000 times exceeding the natural background radiation, on embryogenesis of silkworm, Bombyx mori has been investigated. It is shown that low level ionizing radiation shortens by several hours the period of embryogenesis while the larva mass increases as the development proceeds. A single preincubational exposure of silkworm eggs to a dose of 2 Gy increases the mass of larvae as well as the cocoon shell weight, silk-bearing and the raw silk production.
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Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose.
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Possible reasons for the previously detected inhibitory effect of gamma-radiation (100-1000 Gy in vitro) on isoproterenol-stimulated activity of adenylate cyclase (AC) of the liver plasma membranes of a 20-day-old rat fetus were investigated. It was discovered that the number of beta-adrenergic receptors was reduced. Analysis of basal and fluorine-stimulated activities of AC attests to the radiation-induced damage to catalytic and N-regulatory proteins. The radiation-induced derangement of membrane lipids, where AC functions, is shown.
The transfer of de novo synthesized lipids from microsomes to lipid non-synthesizing membranes was studied in vivo and in vitro from the ratios of specific radioactivities of [14C]cholesterol, [14C] and [32P]phosphatidylcholine and [32P]phosphatidylethanolamine in the nuclei and mitochondria to that in microsomes. The radioactivity of lipids transferred from microsomes to mitochondria and nuclei was identical both in vitro and in vivo and when the lipid-exchange protein of the 105 000 g supernatant was used. Acceleration of lipid metabolism in the liver of gamma-irradiated rats was concomitant with the increase in the rate of labeled cholesterol transfer cation to liver cell nuclei and mitochondria, but remained unchanged in in vitro studies involving lipid-exchange protein. The reduction of phosphatidylethanolamine transfer to the nuclei in vitro and in vivo diminished in the same way. The existence in the cell of mechanisms of transfer of de novo synthesized cholesterol other than lipid-exchange protein is postulated.
The synthesis and phospholipid content in the liver, intestine and spleen in normal and irradiated rats administered ubiquinone-9 were studied with the use of 3H-serine. Ubiquinone markedly activated decarboxylation of phosphatidylserine and suppressed transformation of phosphatidylethanolamine to phosphatidylcholine in rat liver and spleen. The effect was also observed in the organs of irradiated animals. In rat intestine, administration of ubiquinone normalized a sharp gamma-irradiation-induced inhibition of transformation of phosphatidylcholine from phosphatidylethanolamine. The catabolism of phospholipids under the action of ubiquinone and radiation was inhibited in the liver and, on the contrary, was activated in radiosensitive organs.