Document Detail


Increase in urea in conjunction with L-arginine metabolism in the liver leads to induction of cytochrome P450 2E1 (CYP2E1): the role of urea in CYP2E1 induction by acute renal failure.
MedLine Citation:
PMID:  12019204     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of xenobiotics and certain pathophysiological situations cause the induction of CYP2E1. The present study was designed to establish the role of plasma urea nitrogen and L-arginine on hepatic CYP2E1 expression in rats or rats with acute renal failure. Exposure of rats to a single intravenous dose of 5 mg/kg uranyl nitrate caused renal failure in 5 days (ARF), as evidenced by increases in plasma urea nitrogen level and kidney to body weight ratio. Northern and Western blot analyses revealed that hepatic CYP2E1 was 2- to 4-fold induced by ARF. Treatment of rats with either 10% glucose in drinking water for 5 days following a single injection of uranyl nitrate or two injections of recombinant growth hormone (5 units/kg, s.c., twice a day) on the 4th day after uranyl nitrate injection reduced both the rise in plasma urea nitrogen and the induction of CYP2E1. Exposure of rats to urea (approximately 225 mg/kg/day) in drinking water for 1 to 3 day(s) resulted in significant increases in CYP2E1 mRNA and protein. Furthermore, perfusion of the liver with 25 mM urea for 24 h resulted in CYP2E1 induction with an increase in the mRNA. The levels of CYP2E1 protein and mRNA were increased in rats perfused with 25 mM L-arginine for 24 h (i.e., a 4-fold increase). Hence, L-arginine, which is irreversibly hydrolyzed to urea and ornithine by arginase, also induced hepatic CYP2E1. The results of the present study provided evidence that increases in plasma urea in conjunction with L-arginine metabolism lead to the induction of CYP2E1 in the liver.
Authors:
Hye Chin Chung; So Hee Kim; Myung Gull Lee; Sang Geon Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  30     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-05-20     Completed Date:  2002-10-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  739-46     Citation Subset:  IM    
Affiliation:
National Research Laboratory, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, South Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arginine / metabolism*,  pharmacology
Cytochrome P-450 CYP2E1 / biosynthesis*
Enzyme Induction
Glucose / pharmacology
Human Growth Hormone / pharmacology
Kidney Failure, Acute / enzymology,  metabolism*
Liver / enzymology*
Male
Rats
Rats, Sprague-Dawley
Urea / metabolism*,  pharmacology
Chemical
Reg. No./Substance:
12629-01-5/Human Growth Hormone; 50-99-7/Glucose; 57-13-6/Urea; 74-79-3/Arginine; EC 1.14.14.1/Cytochrome P-450 CYP2E1

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