Halothane-induced alterations in cellular structure and proliferation of A549 cells.

Genotoxicity, cytotoxicity or teratogenicity are among the well-known detrimental effects of the volatile anaesthetics. The aim of the present work was to study the structural changes, proliferative activity and the possibility of alveolar A549 cells to recover after in vitro exposure to halothane at 1.5 and 2.1mM concentrations. Our data indicated significant reduction of viability, suppression of mitotic activity more than 60%, and that these alterations were accompanied by disturbances of nuclear and nucleolar structures. The most prominent negative effect was the destruction of the lamellar bodies, the main storage organelles of pulmonary surfactant, substantial for the lung physiology. In conclusion, halothane applied at clinically relevant concentrations exerts genotoxic and cytotoxic effect on the alveolar cells in vitro, most likely as a consequence of stress-induced apoptosis, thus modulating the respiratory function.

Effect of estradiol on the phosphorylation of rat liver ribosome proteins.

The effect of estradiol on phosphorylation with gamma-32P-ATP of ribosome proteins from polyribosome fraction, isolated from female rat liver is found out. Rats (180 g) used were: sham-operated, ovariectomized and treated after ovariectomy for 11 days with 20 micrograms 17 beta-estradiol-dipropionate per 100 g body weight. The estradiol deficiency after ovariectomy decreased phosphorylation, but the estrogenization of ovariectomized rats increases it twice. In vitro the hormone (1-2 mumol/l) [corrected] also stimulated ribosome protein phosphorylation. It is supposed that the hormone may take part in the regulation of protein synthesis in the translational region of the process.

[Effect of estradiol on the synthesis of DNA in the female rat liver]. / Vliianie éstradiola na sintez DNK v pecheni samok krys.

The effect of estradiol on DNA synthesis in hepatocytes was investigated for a study of the functional importance and mechanism of action of sex steroids in the liver. After administration of 17, beta-estradiol dipropionate at a dose of 20 micrograms per 100 g of body mass to ovariectomized albino female rats for 11 days the kinetics of incorporation of 3H-thymidine triphosphate in liver cell nuclei and chromatin was determined. A stimulating effect of the hormone on the tracer incorporation in the nuclei and chromatin was established. A similar tendency was noted in immature female rats. The tracer incorporation depends on the cytosol presence in the system. The rate of incorporation has been shown to increase under the influence of the liver cytosol of intact rats. In can be assumed that estradiol is involved in the regulation of liver DNA synthesis raising matrix activity and modulating cytosol factor activity.

Effect of estradiol on the protein synthesis in the female rat liver in vitro.

The incorporation of 14C-leucine in protein, as well as in aminoacyl adenylate and aminoacyl-tRNA (AA-tRNA) from the liver of mature female rats (controls, ovariectomized and treated after the ovariectomy with daily doses of 20 micrograms 17, beta-estradiol-dipropionate/100 g body weight for 11 days), was investigated under conditions of a cell-free protein-synthesizing system containing isolated microsomes and cytosol. The ovariectomy causes reduced incorporation of the label in protein and in AA-tRNA, while hormonal treatment compensates this decrease either partially or completely. Data are presented which suggest that the hormone probably increases the supply of macroergic components and free amino acids to the hepatocytes, and that it also increases the sensitivity to cycloheximide and tetracycline. It is assumed that estradiol participates in the regulation of the protein synthesis in the hepatocytes at the level of AA-tRNA synthesis.

Binding of cytosol 3H-17, beta-estradiol to cytosol receptors in the liver of female rats.

The article is a study of the specific binding of 3H-17, beta-estradiol to cytosol receptors in the liver of female, sexually mature albino rats: sham-operated, ovariectomized and treated after the ovariectomy with 17-beta-estradiol (in doses of 20 micrograms/100 g body weight for 11 days). The binding of the labelled hormone in the liver cytosol isolated from ovariectomized rats is considerably reduced compared with the sham-operated animals. In the cytosol from the liver of the estradiol-treated rats the formation of a hormone-receptor complex is substantially increased compared with the ovariectomized animals. It is assumed that the formation of estradiol-receptor complexes in the liver depends on the concentration of the cytosol receptors, which is determined by the concentration of oestrogens in the blood.

Effect of estradiol on DNA and protein synthesis in rat liver in vivo.

The article studies the effect of 17, beta-estradiol on the binding of cytosol estradiol-receptor complex with chromatin isolated from the liver of female albino rats (sham-operated, ovariectomized and treated after the ovariectomy with 20 micron hormone/100 g body weight for 11 days) and sexually mature male albino rats. Higher binding of the complex is found for the female animals compared with the males. Parallel experiments are made to study the incorporation of 3H-thymidine and 14C-glycine in vivo, in acid-soluble and acid-insoluble liver fractions of female rats, respectively, which is used as a basis for assessing the rate of DNA and protein synthesis. Ovariectomy induces considerable reduction of the binding of the estradiol-receptor complex with chromatin, as well as of the DNA and protein synthesis. Hormonal treatment of the ovariectomized rats is followed by substantial increase in the parameters investigated above the level measured in intact animals. The observed effects of the hormone on the liver correspond to the accepted view concerning the action of steroid sex hormones on their target organs.