[Hepatobiliary transport of glutathione and its role in cholestasis].

Glutathione is a tripeptide comprised by L-glutamate, L-cysteine, and glycine, that serves antioxygenation and deintoxication functions within the cell. Recent study has found that glutathione is the main driving force for bile salt-independent bile flow, impaired biliary excretion of glutathione can lead to cholestasis. This review focuses on hepatobiliary transport of glutathione and its role in cholestasis. Based on the evidence of choleretic effect of glutathione, enhancement of biliary excretion of glutathione may be a good strategy for prevention and treatment of cholestasis.

[Acute liver failure--medical viewpoints]. / Akutes Leberversagen- Internistische Sicht.

Acute liver failure is a rare disease that can cause death in the majority of untreated cases. Sudden loss of liver function in the absence of a preexisting liver disease is considered the true form and has to be distinguished from impaired function following exacerbation of an underlying liver disease (acute or chronic failure). Common causes include acute viral hepatitis, drug induced liver injury (DILI) and toxins. The loss of the excretory and synthetic function of the liver marks the clinical presentation and results in icterus, coagulopathy and encephalopathy. Additionally impairment of renal function and sepsis occur and contribute to the high mortality of this disease. The activation of cell death mechanisms (apoptosis) leading to a reductio of viable, functional liver tissue is considered to be an important pathophysiologic mechanism. Curative therapy of this disease includes liver transplantation that has been performed in Germany for the first time in 1969. In the year 2004 a total of 91 liver transplantation were performed for acute liver failure (10.3% of all transplants) in German transplant centers.

Phalloidin-induced cholestasis in the rat: relation to changes in microfilaments.

The influence of phalloidin, an agent that causes irreversible polymerisation of actin into microfilaments, on bile secretion and hepatocyte ultrastructure was examined in rats. Phalloidin was given intraperitoneally at the dose of 50 microgram per 100 g of body weight per day for 1, 3, or 7 days. The following was observed. (1) Bile flow decreased, as compared to controls, by 19% after 1 day, 34% after 3 days, and 55% after 7 days. Bile acid secretion was also decreased. (2) Electron microscopic examination of the hepatocyte in treated animals revealed an increased thickness of the pericanalicular microfilamentous network and a dilatation of bile canaliculi. Stereological examination revealed an increase in the relative volume of the microfilamentous network (per unit of hepatocyte cytoplasm) of 2.55% after 1 day, 4.06% ater 3 days, and 6.16% after 7 days. (3) [14C]Erythritol biliary clearance, measured after 7 days, decreased in parallel to bile flow, suggesting that the decrease in bile flow was of canalicular origin. [14C]Sucrose biliary clearance increased in treated animals, suggesting an increased permeability of the biliary system to sucrose. There was a predominant decrease in the bile acid independent bile flow. These data provide circumstantial evidence for the hypothesis that microfilament dysfunction can produce cholestasis.