[Effect of thromboxane B2 on morphological features of apoptosis in cultured rat hepatocytes exposed to hepatotropic substances].

Thromboxanes (TX) are known to have damaging effect on a liver but their influence on the cell death, in particular on hepatocyte apoptosis and its morphological features is not investigated enough. Cell death of the rat hepatocytes was investigated in primary culture by double vital staining with fluorescent nuclear stains Hoechst 33342 and propidium iodide and by electron microscopy. It was established that exogenous Tx B2 increases the amount of hepatocytes with early stages of apoptosis - the condensed chromatin and nucleus and cell size reduction. The changes in a percentage of hepatocytes with morphological features of the late stages of apoptosis - fragmented nuclei and division on apoptotic bodies were not revealed. Tx B2 intensified the carbon tetrachloride action on hepatocyte apoptotic death and increased chromatin condensation. Tx B2 application to hepatocytes injured by chenodeoxycholic acid significantly increased the amount of cells with a final stage ofapoptosis.

[Changes of chromatin structure state in thymocites at the early stage of apoptosis induced by hydrogen peroxide and radiation]. / Zminy strukturnoho stanu khromatynu v tymotsytakh na rann'omu etapi apoptozu za induktsiï peroksydom vodniu i radiatsiieiu.

The paper deals with changes in the structural state of chromatin in isolated thymocites at the early stage of apoptosis induced by hydrogen peroxide and radiation. Content of necrosis and apoptosis cells in the suspension of the isolated rat thymocites, during 3-hour incubation after X-ray irradiation in a dose of 4.5 Gy or with the presence of 0.1 microM of H2O2 by the method of double lifetime staining by fluorescent dye Hehst 33342 and propydium iodide has been estimated. Apoptogenic effect of the studied effects has been found out, the dynamics of condensation and internucleosomic chromatin fragmentation has been established. It has been shown that 100 microM alpha-tocopherol inhibited completely DNA fragmentation in the cells incubated with H2O2 and only partially in irradiated cells. Introduction of postmitochondrial supernatant, isolated from the incubated control or irradiated cells, into the cell-free system which included the ATP-regenerating system and nuclei of control thymocites did not affect the level of DNA fragmentation, while the increase of the level of fragmented DNA in nuclei was observed in the presence of the supernatant obtained by centrifugation of the cells treated by H2O2. Differences of mechanisms of thymocite apoptosis initiation, as affected by hydrogen peroxide and ionizing radiation, is discussed.

[Lipoxygenase inhibitors induce rat hepatocyte apoptosis in primary culture]. / Blokatory lipoksyhenaz indukuiut' apoptoz hepatotsytiv shchuriv u pervynnii kul'turi.

Arachidonic acid metabolites have been shown to have a wide range of effects on cell proliferation and viability. In this study, the effects of lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA) and caffeic acid (CA) on the viability of cultured rat hepatocytes (HC) were investigated. As a result, treatment with NDGA and CA for 4 h and 24 h decreased ALT release from HC and increased a number of apoptotic cells. Apoptosis inducing effects of general LO inhibitor NDGA were more pronounced, than those of 5-LO inhibitor CA. The results suggest that lipoxygenase pathway of arachidonic acid metabolism, in particular 5-LO, is essential regulator of hepatocyte survival and apoptosis.

[Effect of exogenous leukotrienes and lipoxygenase inhibitors on apoptosis and necrosis in cultured rat hepatocytes]. / Vplyv ekzohennykh leikotryieniv i blokatoriv lipoksyhenaz na apoptoz ta nekroz hepatotsytiv shchuriv u pervynnii kyl'turi.

Liver cell death by apoptosis and necrosis occurs upon the liver injury. Lipoxygenase pathway of arachidonic acid metabolism is known to regulate the viability and apoptosis in some cell types, but its role in hepatocyte cell death is not fully understood. We studied the influence of leukotrienes (LT) and lipoxygenase inhibitors on apoptosis and necrosis in rat hepatocyte primary culture by double staining with Hoechst 33342 and propidium iodide and electron microscopy. Treatment with general lipoxygenase inhibitor nordihydoguaiaretic acid and 5-lipoxygenase inhibitor caffeic acid (2. 10(-5) M) for 4 and 24 h induced hepatocyte apoptosis. LTB4 and LTC4 (10(-8) M) decreased the number of living cells and increased the number of necrotic cells. LTs exerted the same necrotic effect on hepatocytes, treated with lipoxygenase inhibitors. It is important that LTs decreased apoptosis induced by inhibitors treatment. These data suggest that lipoxygenase pathway of arachidonic acid metabolism is important regulator of hepatocytes viability and apoptosis The increase of lipoxygenase product formation, in particular LTs, may diminish apoptosis and increase necrosis in hepatocytes upon the liver injury.

[Dynamics of lipid peroxidation in blood and organs of rats after irradiation at low doses and the effect of antioxidants]. / Dynamika perekysovogo okisnennia lipidiv v krovi ta organakh shchuriv za oprominennia v niz'kykh dozakh ta efekt antyoksydantiv.

A study was made of the dynamics of lipid peroxidation (LPO) in rats after the whole-body 1.0 Gy X-irradiation (ten fractions of 0.1 Gy at a 24-hour interval; 0.425 R/min) and the possibility of correction LPO with alpha-tocopherylacetate, ascorbic acid and catechin complex by means of a single and combined administration. The accumulation of primary and secondary LPO products in blood, radiosensitive (spleen and mucosa of small intestine) and radioresistant (brain) organs is established. The administration of mentioned antioxidants diminishes the content LPO products, but does not completely normalize the latter. Administration of antioxidant complex was most effective.