RESUMO
Encephalopathy is an important cause of morbidity and mortality in patients with severe hepatic failure and the mechanisms underlying hepatic encephalopathy are still not fully known. Considering that creatine kinase (CK) play a crucial role in brain energy homeostasis and is inhibited by free radicals, and that oxidative stress is probably involved in the pathogenesis of hepatic encephalopathy, we evaluated CK activity in hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex of rats submitted to acute administration of carbon tetrachloride or acetaminophen. The effects of the administration of antioxidants, N-acetylcysteine (NAC) plus deferoxamine (DFX) in association, and taurine, were also evaluated. Our findings demonstrated that carbon tetrachloride inhibited CK activity in cerebellum; acetaminophen inhibited the enzyme in cerebellum and hippocampus. CK activity was not affected in other brain areas. The administration of NAC plus DFX reversed the inhibition of CK activity caused by carbon tetrachloride in cerebellum and by acetaminophen in cerebellum and hippocampus. On the other hand, taurine was not able to reverse the inhibition in CK activity. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity after hepatic failure may be involved in the pathogenesis of hepatic encephalopathy.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Encéfalo/enzimologia , Intoxicação por Tetracloreto de Carbono/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Creatina Quinase/antagonistas & inibidores , Creatina Quinase/metabolismo , Falência Hepática/enzimologia , Alanina Transaminase/antagonistas & inibidores , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Cerebelo/efeitos dos fármacos , Cerebelo/enzimologia , Metabolismo Energético/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Testes de Função Renal , Falência Hepática/induzido quimicamente , Masculino , Ratos , Ratos WistarAssuntos
Humanos , Animais , Camundongos , Ratos , Toxicologia/educação , Biotransformação/fisiologia , Intoxicação por Tetracloreto de Carbono/enzimologia , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/fisiopatologia , Tetracloreto de Carbono/toxicidade , Células , Sistema Enzimático do Citocromo P-450/efeitos adversos , Fígado/citologia , Modelos BiológicosAssuntos
Humanos , Animais , Camundongos , Ratos , Toxicologia/educação , Tetracloreto de Carbono/toxicidade , Intoxicação por Tetracloreto de Carbono/enzimologia , Intoxicação por Tetracloreto de Carbono/fisiopatologia , Intoxicação por Tetracloreto de Carbono/patologia , Modelos Biológicos , Células/efeitos dos fármacos , Fígado/citologia , Biotransformação/fisiologia , Sistema Enzimático do Citocromo P-450/efeitos adversosRESUMO
The efficacy of silymarin treatment in preventing biochemical and histological alterations in CCL4-induced liver cirrhosis in rats was studied. Four groups of rats were treated with: (1) CCL4; (2) mineral oil; (3) CCL4 + silymarin; and (4) silymarin. All animals were sacrificed 72 h after the end of treatments. The activities of alkaline phosphatase (alk. phosp.), gamma-glutamyl transpeptidase (GGTP), glutamic pyruvic transaminase (GPT) and glucose-6-phosphatase (G6Pase), and bilirubin content were determined in serum. Na+, K+-ATPase and Ca++-ATPase activities were measured in isolated plasma membranes. Lipoperoxidation, triglycerides (TG), and glycogen contents were also measured in liver homogenates. Liver cirrhosis was evidenced by significant increases in liver collagen, lipoperoxidation, serum activities of alk. phosp., GGTP, GPT, G6Pase, bilirubin content, and liver TG. Activities of ATPases determined in plasma membranes were significantly reduced, as was liver glycogen content. Silymarin cotreatment (50 mg/kg b.wt) completely prevented all the changes observed in CCL4-cirrhotic rats, except for liver collagen content which was reduced only 30% as compared to CCL4-cirrhotic rats. Silymarin protection can be attributed to the agent's antioxidant and membrane-stabilizing actions.
Assuntos
Intoxicação por Tetracloreto de Carbono/complicações , Flavonoides/uso terapêutico , Cirrose Hepática Experimental/prevenção & controle , Silimarina/uso terapêutico , Animais , ATPases Transportadoras de Cálcio/metabolismo , Intoxicação por Tetracloreto de Carbono/enzimologia , Colágeno/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/enzimologia , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Endogâmicos , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
In the cholestatic condition of many different aetiologies a common pathologic picture is found. It is characterized by the presence of pigmented "plugs" and cytoplasmatic "masses" in the centrolobular region. Dubin has tried to interpret this on purely hydrostatic ground but this is not a very likely explanation. We tried to comprove this hypothesis studying the interference of a previous, or concomitant, centrolobular alteration in the distribution, morphology and intensity of cholestatic lesions: terminal choledochus ligatures were performed in animals intoxicated with carbon tetrachloride, a substance that damages predominantly the centrolobular region. In 6 dogs, terminal choledochus ligature was associated with carbon tetrachloride intoxication. A histological examination of the liver showed that the degree of centrolobular cholestasis was in the inverse ration of hepatocytic damage intensity. This fact does not conform with Dubin's hypothesis.