[Study of osteoprotective and hypolipidemic effects of estrogen 8α-analogues].

The aim of this work was to study the ability of some estrogen 8α-analogues, that have CH3-group in the C-3 position, exhibit osteoprotective and cholesterolemic effects. The properties of these analogues was comparisoned with effects of native estradiol and 17α-ethynylestradiol (EE). We showed that compounds 3 ((d,l)-17ß-acethoxy-3-methoxy-8α-estra-1,3,5(10)-triene) and 4 ((d,l)-3-methoxy-8α-estra-1,3,5(10)-triene-17-one) had the same osteoprotective and cholesterolemic effects as EE. The utherotropic effects of compound 3 and EE were the same, while the utherotropic activity of 17-keto derivative (compound 4) was higher than effect of EE. The osteoprotective and cholesterolemic effects of compounds 5 and 6 (d- or l-17ß-acethoxy-3-methoxy-13-ethyl-8α-gone-1,3,5(10)-triene) were approximately the same, however the utherotropic action of these compounds was different: the compound 5 had significantly lower activity, but the compound 6 had the same effect in comparison with EE. Thus, all studied estrogen 8α-analogues may be used as basic constructions for structural modifications which is necessary as medications with while spectrum of biological properties.

[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.

[Disruption of nerve tissue cholesterol metabolism in the case of an excess of vitamin A in the growing body]. / Narushenie obmena kholesterina nervnoi tkani pri izbytke vitamina A v rastushchem organizme.

Subcellular distribution and the rate of labelled precursors incorporation into fractions of cholesterol esters were studied in brain and spinal cord of growing rats consuming overdoses of vitamin A. Per os administration of retinyl acetate during 10-16 days of postnatal period at a dose of 1,000 IU resulted in intracellular imbalance of cholesterol content and in distinct increase of cholesterol esters in all the subcellular fractions studied. A decrease of 2-(14)C- acetate incorporation into cholesterol esters of nervous tissue caused by vitamin A overloading was also detected. Analysis of gas chromatograms showed an increase in content of palmitic acid as well as a decrease of unsaturated acids in fractions of cholesterol esters of these animals brain tissues. The impairments of cholesterol metabolism found in nervous tissue of growing body under conditions of retinol overloading may be responsible for deterioration of myelinization.

[Cardiovascular system reactions and bioenergy metabolism in relation to adaptation to apnea]. / Reaktsii serdechno-sosudistoi sistemy i bioénergeticheskii metabolizm v sviazi s adaptatsiei k apnoé.

Responses of the cardio-vascular system and bioenergetic metabolism were studied in the heart tissue in apnoea in naturally adapted to diving musk-rats and unadapted rats and mice. A sharp bradycardia was shown to develop in former animals in arresting a breathing as well an increase in the neutrophils contents in the blood. The data obtained suggest that release of the necessary oxygen and antiradical defence functions can be related to the catalase activity.

[Effect of chronic hyperphenylalaninemia and hypoxia on the effectiveness of the alpha-ketoglutarate shunt in the brain]. / Vliianie khronicheskoi giperfenilalaninemii i gipoksii na éffektivnost' alpha-ketoglutaratnogo shunta v golovnom mozgu.

The effects of hypoxia and chronic hyperphenylalaninaemia (HPA) on the intensity of the alpha-oxoglutarate shunt in rat brain after injection of [5-14C]glutamate were investigated. The reaction of reducing carboxylation of alpha-oxoglutarate was shown to be the rate-limiting step for the whole pathway. The deceleration of this reaction under chronic HPA or, conversely, its increase under short-term heavy hypoxia led to a corresponding decrease or increase of fatty acid synthesis in the brain with [5-14C]glutamate as a radioactive precursor.

[Use of different precursors of fatty acid biosynthesis in the brain in chronic hyperphenylalaninemia]. / Ispol'zovanie razlichnykh predshestvennikov dlia biosinteza zhirnykh kislot v golovnom mozge v usloviiakh khronicheskoi giperfenilalaninemii.

The incorporation of 14C from 2-14C-acetate, 1-6-14C-glucose and 5-14-C-glutamate into fatty acids of brain lipids under chronic hyperphenylalaninemia (HPA) was investigated. A decrease of lipogenesis intensity was demonstrated in young rat brain. In the HPA a decrease in the labelling of fatty acids occurred due to inhibition of the enzymes of fatty acid biosynthesis and to disturbance of metabolic pathways involved in lipogenesis via acentyl-CoA.

[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.