Document Detail


Hypoxia impairs conjugation and elimination of harmol in the isolated perfused rat liver.
MedLine Citation:
PMID:  3559985     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although studies in isolated hepatocytes have demonstrated that hypoxia adversely affects drug conjugation, the impact of hypoxia on drug elimination by conjugation in the intact liver has not been defined. This study in the isolated perfused rat liver examines the effect of acute hypoxia on the hepatic elimination of harmol, a phenolic compound eliminated by conjugation without first undergoing oxidative metabolism. In the preparation used in these experiments, harmol glucuronide is the major metabolite (greater than 80%), with the remainder being sulfate. The hypoxic insult consisted of an 80% reduction of hepatic oxygen delivery for 1 hr. During normal oxygenation, a 20-mumol dose was rapidly eliminated (T1/2 = 4.3 +/- 0.8 min; mean +/- S.D., n = 5). A second dose given after 30 min of hypoxia was eliminated much more slowly (T1/2 = 21 +/- 7.9 min, P less than .01). Upon reoxygenation, T1/2 recovered to 4.2 +/- 0.5 min. Similar effects were observed in steady-state experiments, in which perfusate levels rose from 15.7 +/- 1.3 microM to 31.0 +/- 1.6 microM (P less than .005) during hypoxia, indicating a fall in harmol clearance of at least 50%. In each group of experiments, there was a significant reduction in both the formation and elimination of harmol conjugates during hypoxia. Upon reoxygenation, harmol conjugation recovered, but conjugate elimination remained significantly impaired. The authors conclude that acute hypoxia slows the hepatic elimination of harmol by reducing drug conjugation, an effect that is promptly reversed by reoxygenation.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
P W Angus; G W Mihaly; D J Morgan; R A Smallwood
Related Documents :
1128555 - Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man.
1208675 - Role of cortex in pavlovian discrimination learning.
3420325 - Effect of denervation of carotid labyrinths on breathing in unrestrained xenopus laevis.
1929845 - Cigarette smoking decreases tissue oxygen.
8190405 - The use of inhaled radioisotopes for measuring the effect of sputum induction on trache...
14630475 - The use of accelerometry to detect heel contact events for use as a sensor in fes assis...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  240     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1987 Mar 
Date Detail:
Created Date:  1987-04-27     Completed Date:  1987-04-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  931-6     Citation Subset:  IM; S    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Alkaloids / metabolism*
Anaerobiosis
Animals
Anoxia / metabolism*
Cells, Cultured
Harmine / analogs & derivatives,  metabolism*
Kinetics
Liver / metabolism*
Male
Oxygen Consumption
Rats
Rats, Inbred Strains
Chemical
Reg. No./Substance:
0/Alkaloids; 442-51-3/Harmine; 487-03-6/harmol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Failure of chronic aspirin treatment to inhibit urinary prostaglandin excretion in spontaneously hyp...
Next Document:  Differential effects of hypoxia on the turnover of norepinephrine and epinephrine in the heart, adre...