[Synthesis, structure, and biological properties of some 8alpha-analogues of steroid estrogens with fluorine in position 2].

A total synthesis of 8alpha analogues of steroid estrogens with fluorine in position 2 was achieved. Structural features of these compounds were studied by the example of 17beta-acetoxy-2-fluoro-3-methoxy-8alpha-estra-1,3,5(10)-triene. It was shown that the 8alpha analogues of 2-fluorosubstituted steroid estrogens have a low uterotropic activity and retain the osteoprotective and hypocholesterolemic activities.

[Synthesis and biological properties of 6-oxa-D-homo-8alpha analogues of steroid estrogens].

Modifications of 6-oxa-D-homo-8alpha-analogues of steroid estrogens were found to lead to a complete loss of the uterotropic and hypertriglyceridemic activities. These compounds may be promising for the design on their basis of inhibitors of the steroid hormone metabolism and transporters of other compounds to the estrogen target organs.

[Lipid peroxidation in rabbit and rat visual system structures]. / Perekisnoe okislenie lipidov v strukturakh zritel'nogo trakta krolika i krysy.

In our work, the lipid peroxidation (LPO) in the retina, optic chiasma, and visual cortex of rat and rabbit brain was investigated. The contents of the LPO products (diene conjugates, triene conjugates, TBA-reactive products, Schiff bases) and oxidation index (calculated as 232/2 15) were similar in the retina and visual brain cortex of rats. In vivo, lipid oxidation in the optic chiasma was higher as compared with two other parts of visual tract. The similar data were obtained in our experiments with rabbit's visual tract. The sensitivity of tissues to peroxidation in vitro was studied in homogenates incubated with 0.2 mM ascorbate and 10 mkM FeSO4 for 20 min at 37 degrees C. The results of these experiments deviated from the data obtained in vivo, namely: the LPO in optic chiasma was lower than in the retina and the brain cortex. This data are in compliance with lipid composition of investigated parts of the visual tract of both animals. In our opinion, the high level of LPO in optic chiasma demonstrated in vivo is due to low antioxidants level in this part of the visual tract. Our findings also indicate that LPO in retina both in vivo and in vitro experiments are similar to those in the brain cortex and may be attributed to similar lipid composition and activity of antioxidant enzymes (such as superoxiddismutasa and glutathionereductase).

The effects of thyroxine isomers on free-radical oxidation processes in subcellular fractions of rat cerebral cortex.

Measurements made by chemiluminescence (CL) were used to estimate effective D- and L-thyroxine concentrations and to study their effects on free-radical oxidation processes in the mitochondrial and synaptosomal fractions of rat cerebral cortex in vitro. These experiments showed that in a model system containing riboflavin, the antioxidant activity of D-T4 was 2.2 times greater than that of L-T4. The effective concentrations for the two forms of thyroxine were I50 = 74.3 +/- 7.1 microM for D-T4 and I50 = 154.7 +/- 12.3 microM for L-T4. Studies of the in vitro effects of thyroxine on the membrane fraction of the cerebral cortex were based on luminol-dependent peroxide CL. At physiological concentrations (10 nM), both isomers of the hormone had identical antioxidant activities, which were stronger in the mitochondrial traction, where the intensity of CL decreased by 69% and 66%, compared with 45% and 46% decreases in the synaptosomal fraction. Since the D-form has no hormonal activity, it is suggested that this effect is associated with the phenolic nature of thyroxine.

[Lipogenesis in the brain under hypoxia]. / Protsessy lipogeneza v golovnom mozgy pri gipoksii.

This study investigated the utilization of some radioactive precursors [2(12)C]-acetate, [1-6(14)]-glucose, [5(14)C]-glutamate) for fatty acids and lipid biosynthesis in the rat brain under normal and hypoxic conditions. In severe hemic hypoxia (30-45 min after the injection of 15 mg of NaNO2/100 g body weight) there was a significant increase in 14C incorporation from glutamate into brain lipids (by 2.8 times) and into fatty acids (by 2.2 times) as compared to the control level. Enhanced lipogenesis from glutamate was demonstrated due to the activation of all alpha-ketoglutarate shunt steps. The higher lipogenesis from glutamate in the brain as a possible mechanism for this excitatory amino acid utilization under hypoxia.

[Change in the tricarboxylic acid cycle dehydrogenase activity under the action of thyroxine in the brain of animals of varying age]. / Izmenenie aktivnosti degidrogenaz tsikla trikarbonovykh kislot pod deistviem tiroksina v mozge zhivotnykh raznogo vozrasta.

The effect of thyroxin on the activities of tricarboxylic acid cycle enzymes and NADP-malate dehydrogenase in the rat brain was studied. Experiments were conducted on 20- and 40-day old and on adult rats. Injection of L-thyroxin (50 microgram/100 g body weight) to thyroidectomized rats induced some changes in the activities of citrate-syntase, dehydrogeases of TAC and malic enzymes in the mitochondrial and cytoplasmic fractions of the brain. The most significant effect of the hormone was found in the brain of 20-day old rats there was an increase of the enzyme activities by 40--60%. The effect of the hormone on the enzymes activities could be prevented by simultaneous administration of actinomycin D (10 microgram intracerebrally). This fact indicates that the main mechanism in increasing the enzymic activity lies, probably, in stimulation of the enzyme biosynthesis by the hormone.

[Participation of glutamate and alanine in amino acid biosynthesis, in lipogenesis, and in gluconeogenesis in the brain]. / Uchastie glutamata i alanina v biosinteze aminokislot, v lipogeneze i gliukoneogeneze golovnogo mozga.

The participation of glutamate and alanine in lipogenesis and gluconeogenesis of brain was investigated. 5(14)C glutamate was injected intracisternally in an amount of 5 mcCu/l g tissue and 3(14)C-alanine was injected subcutaneously 30 mcCu/100 g body weight. Labels from glutamate and alanine were recovered in different lipid franctions -- in phospholipids, glycerides, free fatty acids and cholesterol, as well as in glucose and glycogen. An intensive incorporation of label from 5(14)C glutamate into various amino acids--aspartic acid, glutamine, serine, glycine and alanine--was demonstrated. The data presented indicate the participation of amino acids in lipogenesis and gluconeogenesis of brain.

[Mechanisms regulating citric acid metabolism in the brain]. / Mekhanizmy reguliatsii metabolisma limonnoi kisloty v golovnom mozgu.

The changes in the rates of citrate biosynthesis and utilization in rat brain, liver, kidney and heart, produced by hypoxia, action of 2,4-DNP and thyreotoxicosis, were compared with changes of some regulatory parameters under the same conditions. The comparison of citrate-synthase activities, citrate levels in tissues and 14C-incorporation from different precursors into citric acid permitted us to establish that the biosynthesis of citrate in brain was more intensive than in other tissues studied. The main source of acetyl-CoA for citrate-synthase reaction in brain is the oxidation of pyruvate. The ratio of adenine nucleotides plays an important role in the control of citrate-synthase activity in brain, where the oxaloacetate control is not as significant as in liver. NAD-specific isocitrate dehydrogenase reaction was found to be the dominant pathway for citrate oxidation in brain: more than 60 percent of brain citrate were oxidized by NAD-ICDH, while less than 10 percent of citric acid were utilized by this enzyme in other tissues studied. The existance of an adenine nucleotide control of NAD-ICDH activity in brain may be an additional mechanism for the regulation of the first steps of energy metabolism in brain.

[Participation of thyroxine in the regulation of the rate of isocitrate dehydrogenase reactions in the brain and liver]. / Uchaste tiroksina v reguliatsii skorosti izotsitratdegidrogenaznoi REAKTSII v mozge i pecheni

A study was made of the effect of thyroxin on the activity of NAD- and NADP-dependent isocitratedehydrogenases in the brain and the liver of chick embryos. It was found that in both of the organs thyroxin accelerated isocitrate oxidation in the mitochondria through the NAD-dependent route and elevated the velocity of the NADP-isocitratedehydrogenase reaction in the citoplasm. At the same time the activity of the mitochondrial NADP-dependent isocitratedehydrogenase increased after the administration of the hormone to the embryos only in the mitochondria of the brain cells; this was apparently associated with the intensive biosynthesis of specific lipids in the developing brain. There was noted a more marked change in the activity of the enzymes in the 18-day embryos, in comparison with the 12-day ones.

[Change in the activity of NAD- and NADP-specific malate dehyrdogenases in oxygen deficiency in different tissues]. / Izmenenie aktivnosti NAD- i NADF-spetsificheskikh malatdegidrogenaz pri kislorodnoi nedostatochnosti v razlichnykh tkaniakh

NAD-dependent malate dehydrogenase (1.1.1.37) activity was markedly decreased under hypoxia in rat brain and liver mitochondria and cytoplasm; most significant decrease was observed in brain cortex mitochondria. NADP-dependent malate dehydrogenase (1.1.1.40) activity was also reduced under these conditions and the most considerable changes were found in liver mitochondria and cytoplasm. Distribution of activities of these enzymes between subcellular fractions of brain and liver did not change under hypoxia. The oxaloacetate level rised by 20% in brain and decreased by 20-25% in liver under hypoxia.

[Changes in the activities of NAD- and NADP-specific isocitrate dehydrogenases in the brain and liver during the postembryonic development of animals]. / Izmenenie aktivnosti NAD- i NADF-spetsifichnykh izotsitratdegidrogenaz v mozgu i pecheni v khode postémbrional'nogo razvitiia zhivotnykh.

The activities of NAD- and NADP-specific isocitrate dehydrogenases (ICDH) were investigated in subcellular fractions of rat brain and liver. Animals of different age groups were used: newborn, 10-, 20-, 30-, 40-days old and adult rats. It was shown that NAD-ICDH activity rose sharply in adult brain mitochondria as compared with that of developing animals. The NAD-dependent pathway of isocitrate oxidation predominated in mitochondria of both developing and adult brain. The activity of NADP-ICDH decreased in brain mitochondria and cytoplasm in the course of development. Some changes in the distribution of enzyme activity between subcellular fractions were also found in adult brain. The activity of mitochondrial NADP-ICDH was higher than that of newborn animals.