Hepatic oxidative alterations in patients with extra-hepatic cholestasis. Effect of surgical drainage.
OBJECTIVE
The mechanisms of liver injury in conditions of biliary obstruction are poorly understood. Hepatic oxidative injury has been observed in experimental models of cholestasis. Little is known in humans. This study aimed to gain more insights into the hepatic redox status in human cholestasis.


METHODS
Liver concentrations of total glutathione, protein sulfhydryls and malondialdehyde (end-product of lipid peroxidation) were measured in hepatic specimens of 12 patients with obstructive jaundice before and after the application of an external biliary drainage and in six control subjects.


RESULTS
Compared to control subjects, biliary obstructed patients showed significantly (P < 0.001) lower concentrations of hepatic glutathione and protein sulfhydryls, and higher (P < 0.001) levels of malondialdehyde, in the presence of comparable protein concentrations. Two-weeks after the application of external biliary drainage, cholestatic indices were significantly improved and the observed changes in glutathione, protein sulfhydryls and malondialdehyde levels, significantly decreased.


CONCLUSIONS
This study shows that cholestasis is associated with a decreased protein and non-protein sulfhydryl content in the liver and with an increased lipid peroxidation. These alterations reversed almost completely after biliary drainage, indicating the cholestasis itself as the determining factor for the redox status impairment observed in the liver of patients with extra-hepatic biliary obstruction.
Vendemiale
Gianluigi
G
Department of Geriatry and Internal Medicine, University of Foggia, Ospedali Riuniti, Via L Pinto, 71100 Foggia, Italy. g.vendemaile@semeiotica.uniba.it
Grattagliano
Ignazio
I
Lupo
Luigi
L
Memeo
Vincenzo
V
Altomare
Emanuele
E
D000328:Adult; D000368:Aged; D001651:Cholestasis, Extrahepatic / Q000378:metabolism* / Q000601:surgery*; D002784:Cholesterol / Q000097:blood; D004322:Drainage; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000378:metabolism; D000637:Transaminases / Q000097:blood
D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D002784:Cholesterol; D000637:Transaminases; D005978:Glutathione