TY - JOUR
T1 - Hepatic oxidative alterations in patients with extra-hepatic cholestasis. Effect of surgical drainage
AU - Vendemiale, Gianluigi
AU - Grattagliano, Ignazio
AU - Lupo, Luigi
AU - Memeo, Vincenzo
AU - Altomare, Emanuele
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Background/Aims: 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.
AB - Background/Aims: 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.
KW - Biliary drainage
KW - Hepatic glutathione
KW - Malondialdehyde
KW - Obstructive jaundice
KW - Oxidative stress
KW - Protein sulfhydryl
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U2 - 10.1016/S0168-8278(02)00234-9
DO - 10.1016/S0168-8278(02)00234-9
M3 - Article
C2 - 12399225
AN - SCOPUS:0036844813
VL - 37
SP - 601
EP - 605
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 5
ER -