Modelling of formation processes of inclusion complexes of coumarin laser dyes and β-cyclodextrin by the MM2 force field method. I. 7-Amino-4-methylcoumarins

In order to improve the generating and photochemical properties of coumarin laser dyes, the following active media were synthesized: inclusion complexes of -cyclodextrin (-CD) and 7-amino-4-methylcoumarins (COU1, COU102, COU120). Complex formation processes were studied, and the structure of the inclusion complexes was estimated using the method of MM2 molecular mechanics. The data obtained suggest the reasons underlying the complex structure effects on their spectral, luminescent and generating characteristics.     

The influence of gamma-irradiation and alimentry factors on prooxidant-antioxidant rat's liver and blood system

The shift of prooxidant-antioxidant balance in side of prooxidants was revealed in rat liver mitochondria and in microsomes and in blood plasma in response to single irradiation (dose 8 Gy). The shift was more expressed in animals with nutrition unbalanced on animal proteins and antioxidant vitamins. In the main it was explained by the initially reduced activity of enzymatic antioxidant system and especially Se-dependent glutathione peroxidase activity. The apply of food addition from Aronia melanocarpa fruits had delayed lipid peroxidation activation in irradiated animals but practically had no effect on activity of enzymatic antioxidant system. The established essential decrease of Se-dependent glutathione peroxidase activity under unbalanced diet is considered the most crucial point in the maintenance of enzymatic antioxidant system reliability in irradiated animals.     

Antioxidant system activation in rats with experimental cirrhosis after injection of cryopreserved fetal liver cells

The possibility to recover the antioxidant system in rats with experimental liver cirrhosis (LC) after allo- and xenotransplantation of cryopreserved fetal liver cells (FLC) was investigated. It was shown that the content of lipid peroxidation products in the blood serum of animals with LC four weeks after FLC transplantation decreased significantly as compared to control group. Such changes were accompanied by a significant increase of catalase (CAT), glutathione reductase (GR), Se-dependent glutathione peroxidase (GP) activity in the liver and total anti-oxidative activity (AOA) of blood. Obtained results demonstrate that the main direction of FLC effects in animals with LC agree with that we observed previously in other experimental models (partial hepatectomy, chronic alcohol poisoning and hypercholesterolemia). In conclusion, cell therapy may be considered as the universal method for correction of disorders in regulation of free-radical processes in various experimental pathologies.     

Changes in hepatocyte ultrastructure under the influence of chronic furacillin administration to rats]

The ultrastructure of rat liver cells was studied during a 6 months' furacilline (5-nitro-2-furtfurilsemicarbazon) feeding in dose of 40 mg per day, and also during the next 8 months after the treatment cessation. An irregular swelling of membranous structure in addition to disorganization and partial reduction of the granular endoplasmic reticulum were found in the hepatocyte cytoplasm after the prolonged furacilline feeding as well as glycogen depletion and the tendency of the agranular endoplasmic reticulum to enlargement. These changes rarely reached the essential intensity with the transition to necrobiosis. They disappeared already a month after the cessation of furacilline treatment. In all the terms of experiment, the nucleoli were hypertrophied and retained their loose nucleoloneme structure. No sings of furacilline carcinogenic activity were found in rat liver during the 14 months of investigation.     

Lipid peroxidation and regulation of it in rat blood and liver under the experimental alimentary radionuclide effect

Effect of alimentary radionuclide load (137Cs, 700 Bq for animal per day during 7, 14 and 22 days) on the lipid peroxidation intensity and blood and liver enzymatic and non-enzymatic antioxidant system in the Wistar male-rats was investigated. It was found that considerable change of antioxidant system activity in plasma and erythrocytes of experimental animals was already noticeable on the 7th day of radionuclide load. After 22 days of experiment the reliability of glutathione-dependent antioxidant system in blood was essentially decreased and lipid hydroperoxide content was increased. The increase of lipid peroxidation intensity was also found in the experimental animals liver but at the same time the activities of all studied enzymes of antioxidant system were significantly higher than they were in the control rats.     

The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 4. The morphological and ultrastructural changes in the liver of rats]

A study was made of the morphological and ultrastructural changes in hepatic tissue of rats lived within the Chernobyl accident zone during the period of 6 to 25 months. Considerable nonspecific changes in hepatocytes (fatty, vacuolar and parenchymatous degeneration, and hepatocyte necrobiosis) were seen throughout the entire period of observation. Coagulation necrosis of certain hepatocytes, Kupffer and endothelial cells, and the development of microcholangiomas by the end of the second year were the most characteristic alterations.     

The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 3. The morphological and ultrastructural changes in the lungs of rats]

The morphological and ultrastructural changes revealed in the lungs of rats kept within the Chernobyl accident zone during the period of 6 to 24 months were shown to be uniform and multicomponent. The changes were found both in the respiratory and the vascular connective tissue. The inflammatory processes occurred with formation of pneumonic foci, hypo- and disatelectasis, emphysematous changes, impairment of interalveolar septa, and connective tissue cell proliferation. In the lung tissue, focal and diffuse lymphoid proliferates and, at later stages, lymphomatous changes were revealed.     

Effect of visual deprivation on the cytochemical differentiation of neurons in the separate laminae of the rabbit superior colliculus]

The neurons of lamina II, III, VII of the superior colliculus are interferometrically shown to develop features of cytochemical underdevelopment in response to the exclusion of specific visual impulsation. Of the neurons of the lamina studied, lower protein contents in their cytoplasm and nuclei are characteristic, in addition to smaller sizes in comparison with normal ones. A definite specificity of these changes is revealed, which is explained by morphofunctional peculiarities of the neurons of the lamina of the superior colliculus studied.     

Modulation of cellular defense processes in human lymphocytes in vitro by a 1,4-dihydropyridine derivative

The aim of this pilot study was to assess whether a compound of the β-carbonyl-1,4-dihydropyridine series (AV-153 or sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate), which has high efficiency in stimulating DNA repair, can simultaneously modulate apoptosis in human cells. Peripheral blood lymphocytes of healthy donors were used in this study. DNA strand-break rejoining was assessed with the alkaline comet assay after a 3-h incubation of lymphocytes in the presence of a wide range of concentrations of AV-153 (10⁻¹⁰–10⁻⁵ M). Apoptotic and micronucleated (MN) cells were scored in phytohaemagglutinin-stimulated lymphocytes after a 72-h incubation with AV-153, using the standard cytokinesis-blocked micronucleus test. The study revealed dual effects of AV-153 on cellular defense systems against endogenously generated DNA damage: the compound per se simultaneously reduces DNA strand breaks and stimulates apoptosis, with a maximal efficiency of 76% and 42%, respectively; in contrast, after genotoxic stress (2 Gy of gamma-radiation) AV-153 reduces DNA strand breaks, the number of MN cells and apoptotic cells in a similar dose-dependent manner. A maximal efficiency of 67% was found for reduction of DNA strand breaks, while for MN cells and apoptotic cells the efficiencies were, respectively, 47% and 44%. While limited in number, these preliminary studies show the direct correlation between the efficiency of AV-153 in reduction of radiation-induced DNA breaks and MN cells on one side, and in reduction of apoptosis on the other. It suggests that the major target of the compound's action on genotoxic stress is DNA repair, followed by reduction of the number of damaged cells entering apoptosis.     

Metabolism of heme and hemoproteins in rat liver upon administration of mercuric chloride

Rat liver delta-aminolevulinate synthase (delta-ALAS) activity in the early period after mercury chloride administration (0.7 mg per 100 g body weight) was found to be followed by free heme level increase, which was registered by the increase of heme saturation of the heme-binding protein tryptophan-2,3-dioxygenase (T-2,3-DO). delta-ALAS and heme oxygenase activity increase was observed 24 h after action. Microsomal cytochromes P450 and b5 levels decrease. Heme saturation of the T-2,3-DO returned to control level. Heme oxygenase and T-2,3-DO induction promoted hepatocytes free heme level normalization. Heme oxygenase and delta-ALAS induction role in the liver cells defense from the oxidative damage is discussed.