Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Alcohol Clin Exp Res ; 24(4 Suppl): 59S-63S, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10803782

RESUMO

BACKGROUND: We examined the effects of glutathione depletion on the level of superoxide anion released into hepatic sinusoids after lipopolysaccharide challenge. METHODS: Rats were given 1 mg/kg of maleic acid diethyl ester to deplete glutathione in vivo and then 0.5 mg/kg body weight of lipopolysaccharide. RESULTS: This treatment significantly depleted serum reduced glutathione (32.7 +/- 1.7 vs. 23.0 +/- 3.2 mM, p = 0.002). However, it did not affect the serum oxidized glutathione concentration (2.88 +/- 0.56 vs. 3.10 +/- 0.78 mM, not significant). The lipopolysaccharide challenge caused significant superoxide anion formation as compared with controls (0.12 +/- 0.04 vs. 0.22 +/- 0.05 o.d., p < 0.001), and it was enhanced significantly by glutathione depletion (0.28 +/- 0.04 o.d., p < 0.05). There were no significant differences in levels of lipopolysaccharide (2142 +/- 452 vs. 2503 +/- 612 pg/ml) and tumor necrosis factor alpha (277 +/- 186 vs. 252 +/- 88 pg/ml) after the lipopolysaccharide challenge between the glutathione-depleted and nondepleted rats. Moreover, the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in liver perfusates, a marker of damage to endothelial cells in hepatic sinusoids, was significantly higher in the glutathione-depleted rats than in the nondepleted rats. CONCLUSIONS: The reduced form of glutathione can decrease levels of the superoxide anion released into hepatic sinusoids and can decrease subsequent damage to endothelial cells in these sinusoids caused by lipopolysaccharide; that is, it can reduce lipopolysaccharide-induced liver injury.


Assuntos
Glutationa/sangue , Lipopolissacarídeos/farmacologia , Fígado/irrigação sanguínea , Superóxidos/metabolismo , Animais , Ânions , Cinética , Lipopolissacarídeos/sangue , Masculino , Maleatos/farmacologia , Oxirredução , Ratos , Ratos Wistar , Espectrofotometria , Fator de Necrose Tumoral alfa/análise
3.
J Hepatol ; 31(2): 235-41, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10453935

RESUMO

BACKGROUND/AIMS: The aim of this study was to determine whether the spleen contributes to superoxide anion release into the hepatic sinusoids and subsequent damage to endothelial cells of the hepatic sinusoids after lipopolysaccharide challenge. METHODS: Rats were given 2 mg/kg body weight lipopolysaccharide. Three hours after the treatment, superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome C method. Damage to endothelial cells of the hepatic sinusoids was assessed from the purine nucleoside phosphorylase/glutamic-pyruvic transaminase ratio in the liver perfusate. To further characterize the mechanisms behind these changes, these studies were done in rats given superoxide dismutase or an anti-TNFalpha antibody. To study whether the spleen plays a role in the mechanisms, experiments with splenectomized rats were performed. RESULTS: Lipopolysaccharide challenge resulted in superoxide anion release into the hepatic sinusoids and damage to endothelial cells of the hepatic sinusoids. These changes were significantly attenuated by the treatments with superoxide dismutase or an antibody against TNFalpha, as well as by splenectomy. The hepatic macrophage and Kupffer cell populations after lipopolysaccharide challenge were significantly smaller in the rats given splenectomy than in those given a sham operation. There were no significant differences in the neutrophil populations between the two groups. Levels of TNFalpha were significantly lower in the former than the latter, whereas there were no significant differences in levels of Interleukin-8 between the two groups. CONCLUSIONS: Splenectomy reduced the superoxide anion release into the hepatic sinusoids caused by the lipopolysaccharide challenge and subsequent damage to endothelial cells of the hepatic sinusoids. This supports the view that splenectomy has a protective effect in lipopolysaccharide-induced liver injury.


Assuntos
Capilares/metabolismo , Fígado/metabolismo , Baço/metabolismo , Esplenectomia , Superóxidos/metabolismo , Animais , Capilares/patologia , Grupo dos Citocromos c , Células de Kupffer/metabolismo , Lipopolissacarídeos/efeitos adversos , Fígado/patologia , Macrófagos/metabolismo , Masculino , Ratos , Ratos Wistar
4.
Alcohol Clin Exp Res ; 23(4 Suppl): 71S-75S, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10235283

RESUMO

Superoxide anion release into the hepatic sinusoids and subsequent damage to the endothelial cells of the hepatic sinusoids after ethanol challenge was examined. A 250 mg/kg body weight/hr dose of ethanol was given to rats for 3 hr, and superoxide anion release into the hepatic sinusoids was examined in a liver perfusion model using the cytochrome c method. Ethanol treatment resulted in superoxide anion release into the hepatic sinusoids (0.20 +/- 0.01 vs. 0.12 +/- 0.02 o.d., p < 0.05) and an increase in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate, a marker of damage to the endothelial cells of the hepatic sinusoids (0.003 +/- 0.002 vs. 0.008 +/- 0.002; p < 0.05). Tumor necrosis factor-alpha was not detectable in either group, and there were no significant differences in the population of hepatic macrophages, leukocytes, or Kupffer cells between the two groups. To clarify the role of Kupffer cells in the mechanism, 10 mg/kg of body weight of gadolinium chloride was given to rats twice, 24 hr apart, resulting in depletion of ED2-positive cells from the hepatic lobules. The superoxide anion release after the ethanol challenge was significantly attenuated in the Kupffer cell-depleted rats, compared with the controls (0.14 +/- 0.02; p < 0.05, compared with ethanol alone). The change was associated with a significant decrease in the purine nucleoside phosphorylase/alanine aminotransferase ratio in the liver perfusate (0.004 +/- 0.002; p < 0.05, compared with ethanol alone). Ethanol causes superoxide anion release into the hepatic sinusoid and subsequent damage to the sinusoidal endothelial cells. These changes were reduced by Kupffer cell depletion. This supports the view that Kupffer cell depletion has a protective effect on ethanol-induced liver injury.


Assuntos
Etanol/toxicidade , Células de Kupffer/fisiologia , Fígado/irrigação sanguínea , Superóxidos/sangue , Alanina Transaminase/metabolismo , Animais , Ânions , Anti-Inflamatórios/farmacologia , Contagem de Células , Endotélio Vascular/patologia , Gadolínio/farmacologia , Células de Kupffer/efeitos dos fármacos , Hepatopatias Alcoólicas/patologia , Masculino , Purina-Núcleosídeo Fosforilase/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/análise
5.
Alcohol Clin Exp Res ; 23(4 Suppl): 92S-95S, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10235287

RESUMO

Ethanol oxidation in Kupffer cells was investigated by measuring 14C-acetate formation from 14C-ethanol, and the role of aldehyde dehydrogenase 2 (ALDH2) in this process was also examined. Formation of 14C-acetate from 20 mM of 14C-ethanol was significantly increased in medium-containing Kupffer cells (9,003 +/- 2,066 cpm/5 x 10(6) cells), compared with medium containing no cells (1,826 +/- 46 cpm, p < 0.01), or containing acid-killed Kupffer cells (1,629 +/- 210 cpm, p < 0.01). Ethanol formation was significantly attenuated when 20 and 200 microM cyanamide or 2 microM disulfiram were given. Reverse transcriptase-polymerase chain reaction demonstrated that Kupffer cells carry mRNA for ALDH2. These findings indicate that Kupffer cells can oxidize ethanol to acetate. ALDH2 may participate in this process, especially in the conversion of acetaldehyde to acetate.


Assuntos
Etanol/metabolismo , Células de Kupffer/metabolismo , Acetaldeído/metabolismo , Acetatos/metabolismo , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Animais , Radioisótopos de Carbono , Cianamida/farmacologia , Dissulfiram/farmacologia , Inibidores Enzimáticos/farmacologia , Células de Kupffer/efeitos dos fármacos , Masculino , Oxirredução , RNA Mensageiro/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
Alcohol Clin Exp Res ; 22(S3 Pt 1): 129S-132S, 1998 05.
Artigo em Inglês | MEDLINE | ID: mdl-9622389

RESUMO

Endotoxin is postulated to be an important aggravating factor for alcoholic liver disease. We have previously reported that rats fed ethanol are more vulnerable to endotoxin-induced liver damage, and hepatic microcirculatory disturbance plays an important role for this liver damage by observation with an intravital microscopy. In this study, we have investigated the role of adhesion molecules in endotoxin-induced microcirculatory disturbance in chronic ethanol-fed rats. Male Wistar rats were pair-fed with ethanol liquid diet (ethanol group) or an isocaloric control diet (control group) for 6 weeks. Leukocyte adherence to the hepatic sinusoid by stimulation with lipopolysaccharides (1 mg/kg of body weight) was observed by an inverted fluorescence microscopy equipped with a silicon-intensified target camera and was found to be enhanced in ethanol-fed rats. Tumor necrosis factor-alpha and GRO/CINC-1 (rat counterpart of interleukin-8) was increased in the blood in these animals. Subsequent expression of adhesion molecules, LFA-1 beta-chain on leukocytes were demonstrated by flow cytometry, which suggests a possible involvement of leukocyte adherence to the hepatic damage in ethanol-fed animals. Preadministration of anti-rat LFA-1 beta-chain monoclonal antibody effectively suppressed leukocyte adherence to the hepatic sinusoid. These results suggest that the enhanced sequestration of neutrophils to the liver with these adhesion molecules may play a significant role in the pathogenesis of alcoholic liver disease.


Assuntos
Alcoolismo/imunologia , Moléculas de Adesão Celular/fisiologia , Endotoxemia/imunologia , Leucócitos/imunologia , Hepatopatias Alcoólicas/imunologia , Fígado/irrigação sanguínea , Animais , Lipopolissacarídeos/imunologia , Masculino , Microcirculação/fisiopatologia , Microscopia de Fluorescência , Ratos , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...