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In patients with cirrhosis, the elimination of drugs metabolized by glucuronidation is relatively preserved, in comparison with the metabolism of drugs by oxidation. This study explores this phenomenon at a molecular level. In cirrhotic rat livers the content of UDP-glucuronosyltransferase (UGT) was examined by immunohistochemistry and immunoblotting using three antibodies: (i) a polyclonal antibody directed against a broad number of UGT isoforms from both family 1 and family 2; (ii) a family 2-specific antibody; and a (iii) family 1-specific antibody. The steady state mRNA level of UGT of a family 2 isoform was also detected by northern blot analysis. The results demonstrate normal or increased UGT protein by immunohistochemistry and immunoblot in cirrhotic livers compared with controls. This was accompanied by increased steady state mRNA encoding the UGT isoform UGT2B1. In contrast, an isoform of cytochrome P450 (CYP2C11) was reduced markedly in both immunohistochemical staining and immunoblot analysis. These results suggest that in cirrhosis there is a comparative increase or at least a maintenance of UGT enzyme content and that this most likely occurs at a pretranslational level.
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
December 1996,
Journal of gastroenterology and hepatology,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
September 1995,
Annals of the New York Academy of Sciences,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
April 1983,
European journal of biochemistry,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
December 1986,
Molecular pharmacology,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
January 1986,
Hepatology (Baltimore, Md.),
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
February 1977,
The Journal of biological chemistry,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
August 1982,
Research communications in chemical pathology and pharmacology,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
June 1981,
Biochemical pharmacology,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
December 2008,
Biochemical and biophysical research communications,
H S Debinski, and
P I Mackenzie, and
C S Lee, and
M L Mashford, and
J A Danks, and
T R Tephly, and
M Green, and
P V Desmond
March 1975,
Biochimica et biophysica acta,
