EFFECT OF CYTOCHROMES P450 CHEMICAL INHIBITORS AND MONOCLONAL ANTIBODIES ON HUMAN LIVER MICROSOMAL ESTERASE ACTIVITY

2006 ◽  
Vol 34 (8) ◽  
pp. 1361-1366 ◽  
Author(s):  
Stacey L. Polsky-Fisher ◽  
Hong Cao ◽  
Ping Lu ◽  
Christopher R. Gibson
2013 ◽  
Vol 2013 ◽  
pp. 1-24 ◽  
Author(s):  
Ling Ye ◽  
Xiao-Shan Yang ◽  
Lin-lin Lu ◽  
Wei-Ying Chen ◽  
Shan Zeng ◽  
...  

Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a toxic herb that can frequently cause fatal cardiac poisoning.Aconitumtoxicity could be decreased by properly hydrolyzing diester-diterpene alkaloids into monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are the primary active and toxic constituents of processedAconitum. Cytochrome P450 (CYP) enzymes protect the human body by functioning as the defense line that limits the invasion of toxicants. Our purposes were to identify the CYP metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish which isozymes are responsible for their metabolism through the use of chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution mass spectrometry was used to characterize the metabolites. A total of 7, 8, and 9 metabolites were detected for BAC, BMA, and BHA, respectively. The main metabolic pathways were demethylation, dehydrogenation, demethylation-dehydrogenation, hydroxylation and didemethylation, which produced less toxic metabolites by decomposing the group responsible for the toxicity of the parent compound. Taken together, the results of the chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4 and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA.


Xenobiotica ◽  
2016 ◽  
Vol 47 (4) ◽  
pp. 324-331 ◽  
Author(s):  
Michaela Kopečná-Zapletalová ◽  
Kristýna Krasulová ◽  
Pavel Anzenbacher ◽  
Petr Hodek ◽  
Eva Anzenbacherová

2009 ◽  
Vol 8 (4) ◽  
pp. 1672-1681 ◽  
Author(s):  
Cathrin Seibert ◽  
Brian R. Davidson ◽  
Barry J. Fuller ◽  
Laurence H. Patterson ◽  
William J. Griffiths ◽  
...  

1998 ◽  
Vol 8 (5) ◽  
pp. 375-382 ◽  
Author(s):  
Tian J. Yang ◽  
Yang Sai ◽  
Kristopher W. Krausz ◽  
Frank J. Gonzalez ◽  
Harry V. Gelboin

1989 ◽  
Vol 8 (2) ◽  
pp. 61-94 ◽  
Author(s):  
Lucy M. Anderson ◽  
Jerrold M. Ward ◽  
Sang S. Park ◽  
Jerry M. Rice

2005 ◽  
Vol 149 (2) ◽  
pp. 349-351 ◽  
Author(s):  
Eva Anzenbacherova ◽  
Jakub Janalik ◽  
Igor Popa ◽  
Miroslav Strnad ◽  
Pavel Anzenbacher

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