Assuntos
DNA/biossíntese , Vírus de Hepatite , Hepatite Animal/metabolismo , Fígado/metabolismo , Biossíntese de Proteínas , RNA/biossíntese , Animais , Fracionamento Celular , Nucléolo Celular/metabolismo , Centrifugação com Gradiente de Concentração , Citoplasma/metabolismo , RNA Polimerases Dirigidas por DNA/metabolismo , Hepatite/enzimologia , Fígado/enzimologia , Fígado/patologia , Camundongos , Ácido Orótico , Polirribossomos/metabolismo , RNA Mensageiro/metabolismo , RNA Ribossômico/metabolismo , Frações Subcelulares/metabolismo , Fatores de Tempo , Trítio , UltrassomRESUMO
Pretreatment of mice with silymarin dihemisuccinate sodium salt (SHS-Na) 300 mg/kg 24 and 16 h before infection completely protected against the lethal effect of Frog Virus 3 (FV3). After the inoculation of 1 LD100 of virus it could be shown that: a) the same amount of radioactively labelled virus was found in the liver of control and SHS-Na treated animals, b) in SHS-Na pretreated animals the shut-off of macromolecular syntheses in the liver was considerably less extensive, c) the histological changes in the hepatocyte nuclei were attenuated in SHS-Na pretreated animals and the serum titer of the transaminases did no increase, d) in SHS-Na pretreated mice there were only limited functional alterations of the sinusoidal cells as studied by carbon phagocytosis and the serum titer of the lysosomal enzymes was only slightly modified, e) inhibition of protein synthesis during the period of pretreatment with SHS-Na did not decrease the level of protection. These results allow us to conclude that SHS-Na exerts its protective effect on the liver and that sinusoidal cells are most likely involved in this protection.
Assuntos
Flavonoides/uso terapêutico , Hepatopatias/prevenção & controle , Silimarina/uso terapêutico , Viroses/prevenção & controle , Animais , Feminino , Iridoviridae , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Camundongos , Necrose , Biossíntese de Proteínas , RNA/biossíntese , Silimarina/análogos & derivados , Viroses/metabolismo , Viroses/patologiaRESUMO
The i.p. or i.v. injection of frog virus 3 (FV3) in mice produces a hepatitis which leads to the death of the animals within 24 h. This hepatitis is of a purely toxic nature since the virus does not develop at 37 degrees C. The toxic effect of the virus, which can be differentiated from the infectious effect, involves one or more structural proteins. The first pathological changes occur during the first few hours after the injection in the vicinity of the nuclei of the liver parenchyma cells in the form of changes in the chromatin and nucleoplasm. The inhibition of the synthesis of cellular macromolecules and of the function of nuclear enzymes points to the fact that it is the nucleus that is first and foremost attacked. Necrosis and biochemical disturbances in the vicinity of the cytoplasm appear later on. Premedication of the mice with a water-soluble silymarin salt leads to a distinct rise in the survival rate of the animals. The protective function of silymarin is dependent on the dose and on the duration of the premedication. The LD50 of FV3 in those mice which had previously been given silymarin, is approximately three times that of the animals which received no premedication.