Relationship between content of hepatic glutathione S-transferases and the kinetics of indocyanine green elimination in various liver diseases.
The glutathione (GSH) S-transferases are believed to have dual functions as hepatic detoxifying enzymes and intrahepatic binding proteins. Little is known about their alterations in human liver diseases. Therefore, we have studied the relationship between the enzyme activity and rose bengal (RB) binding in hepatic cytosol and plasma indocyanine green (ICG) kinetics in patients with various liver diseases. The enzyme activity was measured in samples of hepatic cytosol obtained from 52 patients. In addition, the content of cationic and neutral transferases was estimated in 17 biopsy samples by densitometry of Coomassie blue stained sodium dodecyl sulphate polyacrylamide gel electrophoretograms. RB binding studies also were performed on cytosol samples. ICG kinetic parameters were determined using the two-compartment open model in 17 patients who were given the dye (0.5 mg kg-1) intravenously. Correlations between the enzyme activity and liver function tests, content of the enzyme, RB binding and ICG kinetic parameters were evaluated. The following results were obtained. (1) The enzyme activities were high in alcoholic liver disease, fatty liver and Gilbert's syndrome, and low in cirrhosis. (2) The enzyme activities were positively correlated with serum cholinesterase activity, serum albumin level and hepaplastin test, and negatively correlated with ICG retention rate at 15 min. (3) The enzyme activity, its content and RB binding affinity of the cytosol were positively correlated with each other. (4) The enzyme activity was positively correlated with hepatic ICG distribution volume. These results are consistent with the role of the GSH S-transferases as ligandins in intracellular storage of dyes.
Sugimoto
M
M
Second Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
Shimada
N
N
Aikawa
K
K
Sugiyama
Y
Y
D002759:Adenoma, Bile Duct / Q000201:enzymology; D001650:Bile Duct Neoplasms / Q000201:enzymology; D001653:Bile Ducts, Intrahepatic; D002802:Cholinesterases / Q000097:blood; D003110:Colonic Neoplasms / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004589:Electrophoresis, Disc; D005982:Glutathione Transferase / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008111:Liver Function Tests; D012016:Reference Values; D012395:Rose Bengal / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology
D012395:Rose Bengal; D005982:Glutathione Transferase; D002802:Cholinesterases; D007208:Indocyanine Green