Alteraçöes näo desacopladoras da fosforilaçäo oxidativa mitocondrial na colestase extra-hepática / Non uncoupling alterations of mitochondrial oxidative phosphorylation in extrahepatic cholestasis

Estudou-se 28 ratos machos Wistar com peso entre 200 e 250 g. divididos em dois grupos: Controle (n = 14) e grupo com obstruçäo biliar extra-hepática OBE) (n = 14). O grupo OBE os animais foram submetidos a ligadura dupla do ducto hepático (dh) para induçäo da obstruçäo biliar. O grupo controle foi submetido apenas a cirurgia fictícia para ligadura do dh. O período de observaçäo foi de sete dias, após o que foram sacrificados por exsanguinaçäo. O estudo da funçäo mitocondrial mostrou que os ratos do grupo OBE apresentaram razäo de controle respiratório mitocondrial (RCR) e respiraçäo ativada (estado III) diminuidas significativamente (P < 0,05) em comparaçäo ao grupo controle. A respiraçäo basal (estado IV) foi semelhante em ambos os grupos . Houve aumento significativo das bilirrubinas (total e fraçöes) e fosfatase alcalina no grupo OBE em relaçäo ao grupo controle (P < 0,05). Em conclusäo, o desacoplamento da fosforilaçäo oxidativa mitocontrial descrita na literatura, näo foi observada no presente estudo

Effects of warm and cold ischemia on mitochondrial functions in brain, liver and kidney.

The purpose of this work was to study the effects of warm (37 degrees C) and cold (4 degrees C) ischemia on different mitochondrial functions in rat brain, liver and kidney. After 10 to 60 minutes of ischemia at 37 degrees C the energy coupled respiration as well as the ADP-induced malate-aspartate shuttle activity in brain and liver mitochondria or the rate of mitochondrial ATP synthesis in kidney were significantly decreased. However, the respiratory rates and the shuttle activity in the absence of ADP remained unchanged. These data suggest that ischemia primarily affects electron transport in the respiratory chain rather than the hydrogen shuttle and the energy coupling system. When the temperature during the indicated ischemic periods was decreased to 4 degrees C, in brain and liver no significant alterations of these mitochondrial functions were found in comparison with the non-ischemic controls. When rat kidneys were stored for 36 hours at 4 degrees C according to Collins mimicking transplantation conditions, the mitochondrial respiration and ATP synthesis were only slightly decreased. It therefore appears that hypothermia can prevent effectively mitochondrial dysfunction due to ischemia.

Influence of hypoxia on mitochondrial function and energy status in CCl4-induced cirrhotic rat liver.

The influence of hypoxia on hepatic mitochondrial function and energy status was studied in normal and carbon tetrachloride (CCl4)-induced cirrhotic rats. Under hypoxemia of 50 mm Hg-PaO2, hepatic energy status was suppressed both in normal and cirrhotic rats. After the reversal of hypoxia, it was completely restored in normal rats concomitant with a rapid elevation of hepatic mitochondrial redox state (overshoot phenomenon) and increase in the mitochondrial oxidative phosphorylative activity. By contrast, in cirrhotic rats, such an enhancement of mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondrial function was not observed. It was clarified that cirrhotic liver mitochondria have little capacity to respond to the hypoxic stress. A lower resistance to hypoxic episode in cirrhotics might be attributable to the absence of mitochondrial enhancement which is a compensatory mechanism for the deranged energy metabolism of the liver.

[Experimental study on therapeutic plasmapheresis with the biliary decompression in the treatment of obstructive jaundice].

The effectiveness of therapeutic plasmapheresis with the biliary decompression was evaluated using animal model in the treatment of obstructive jaundice. Plasma exchange (PE) using fresh frozen plasma was carried out with biliary decompression on canine jaundice model made by means of ligation and resection of bile duct. Routine biochemical analysis was performed following the PE and biliary drainage and the result was compared with the external biliary drainage group. Plasma level of total bilirubin decreased after PE and kept lower level while plasma level of bilirubin in external biliary drainage group decreased slowly. M-GOT and GOT level, those are the indicators of liver cell injury, was lower in PE group. Mitochondrial function of liver cell was evaluated following partial hepatectomy carried out two days after PE with biliary decompression on jaundiced rat. Mitochondrial respiratory control ratio and ADP/O ratio was improved in PE group. The effectiveness of PE is speculated as the combined mechanism of the removal of hepatotoxic factors in the jaundiced plasma and the addition of hepatotrophic factors within the fresh frozen plasma. These results support the effectiveness of PE to shorten the biliary drainage period and to improve the hepatic function for perioperative management.

Funçäo mitocondrial do fígado na colestase extra-hepática: efeito da clorpromazina / Liver mitochondrial function in the extrahepatic cholestasis: effect of the clorpromazine

Estudou-se 56 ratos machos Wistar com peso entre 200 a 250g divididos em quatro grupos de quatorze cada um. Quatorze ratos foram submetidos à ligadura dupla do ducto hepático para induçäo da obstruçäo biliar extra-hepática (grupo O). Quatorze ratos com obstruçäo biliar extra-hepática (grupo Oc), administrou-se cloridrato de clorpromazina (CPZ) (10mg/Kg peso corpóreo/dia). Os animais do grupo O e Oc foram comparados com animais controles submetidos à cirurgia fictícia para obstruçäo biliar extra-hepática sem CPZ (grupo C) e com CPZ (grupo Cc). O período de observaçäo foi de 7 dias. Os ratos colestáticos apresentaram aumento de bilirrubinas total e fraçöes, fosfatase alcalina e alanino-aminotransferase (ALT) e diminuiçäo da funçäo mitocondrial em comparaçäo com o grupo controle (P<0,05). A CPZ administrada nos animais colestáticos (Oc), diminuiu os valores da ALT (P<0,05 vs O) e melhorou a funçäo mitocondrial (P<0,05 vs O). Como os valores das bilirrubinas e fosfatase alcalina foram semelhantes em ambos os grupos (F>0,05 O vs.Oc), é possível supor que a açäo desta droga ocorreu em algum ponto da estrutura mitocondrial e da membrana citoplasmática, independente da açäo das bilirrubinas, provavelmente lesadas pela isquemia hepática

Liver mitochondria from manganese-deficient and pallid mice: function and ultrastructure.

Oxidative phosphorylation was studied in isolated liver mitochondria from manganese-deficient mice and in those from a mutant strain, pallid. In mitochondria from manganese-deficient mice, ratios of adenosine triphosphate formed to oxygen consumed were normal, but oxygen uptake was reduced. Electron microscopy of these mitochondria revealed ultrastructural abnormalities including elongation and reorientation of cristae. No biochemical or structural abnormalities were found in mitochondria from pallid mice.