Document Detail


Inhibition of rat liver aldehyde dehydrogenase by carbon tetrachloride.
MedLine Citation:
PMID:  7299699     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Current data suggests that aldehydic products of lipid peroxidation possess substantial cytotoxic properties. Carbon tetrachloride (CCl4), a potent stimulator of hepatic lipid peroxidation, was tested for possible effects on hepatocellular aldehyde metabolism. CCl4 (1 ml/kg) produced an elevation in serum alanine aminotransferase activity, hepatic fatty infiltration, centrilobular necrosis and significant decreases in the content of hepatic microsomal cytochrome P-450. Concurrently, the aldehyde dehydrogenase (E.C. 1.2.1.3) activity of mitochondrial and cytosolic fractions was significantly depressed. The lower Km aldehyde dehydrogenase located in the mitochondria showed the largest degree of inhibition (46%). An in vitro system which contained the low Km mitochondrial aldehyde dehydrogenase was employed to determine the role of microsomal lipid peroxidation in the inhibition of the enzyme. Aldehyde dehydrogenase was shown to be extremely sensitive to inhibition under conditions of NADPH or NADPH and CCl4-stimulated lipid peroxidation. Reduced glutathione (6 mM) provided complete protection of aldehyde dehydrogenase activity under conditions of NADPH-stimulated lipid peroxidation but could not protect activity loss during CCl4-stimulated microsomal lipid peroxidation. The degree of enzyme activity loss related well with the amount of thiobarbituric reacting substances present in the incubation mixture. These findings show that CCl4 decreases the activity of the aldehyde oxidizing enzyme, aldehyde dehydrogenase. This effect may accentuate cytotoxic effects of reactive aldehydic products generated during lipid peroxidation.
Authors:
J J Hjelle; J H Grubbs; D G Beer; D R Petersen
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  219     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1981 Dec 
Date Detail:
Created Date:  1982-01-28     Completed Date:  1982-01-28     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  821-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Dehydrogenase
Aldehyde Oxidoreductases / antagonists & inhibitors*
Animals
Body Weight / drug effects
Carbon Tetrachloride / pharmacology*
Cytochrome P-450 Enzyme System / metabolism
Lipid Peroxides / metabolism
Liver / drug effects,  enzymology*
Male
NADP / metabolism
Organ Size / drug effects
Rats
Rats, Inbred Strains
Subcellular Fractions / drug effects,  enzymology
Grant Support
ID/Acronym/Agency:
03527//PHS HHS
Chemical
Reg. No./Substance:
0/Lipid Peroxides; 53-59-8/NADP; 56-23-5/Carbon Tetrachloride; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.2.-/Aldehyde Oxidoreductases; EC 1.2.1.3/Aldehyde Dehydrogenase

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


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