Linked Life Data

2390105

Source:http://linkedlifedata.com/resource/pubmed/id/2390105

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1990-9-27
pubmed:abstractText
The influence of ciprofibrate, a potent oxyisobutyrate derivative, on several hepatic enzyme parameters was studied in five rat strains following a 14-day treatment period. Ciprofibrate-dependent hepatomegaly was observed at two dose levels (2 and 20 mg/kg) in all rat strains examined. A 10- to 15-fold induction in the 12-hydroxylation of lauric acid with a less marked 1.5- to 5-fold induction of 11-hydroxylation was observed in treated animals. This dose-dependent increase in fatty acid hydroxylase activity was associated with a maximal 10-fold increase in the specific content of cytochrome P-450 IVA1 isoenzyme apoprotein, as assessed immunochemically using an ELISA technique. The activities of the cytochrome P-450 I (IA1 and IA2) and II (IIB1 and IIB2) families, as measured by ethoxyresorufin-O-deethylase and benzphetamine-N-demethylase activities respectively, were decreased on treatment. In the mitochondria, monoamine oxidase activity was significantly decreased at the higher dose level whereas alpha-glycerophosphate dehydrogenase activity was elevated. Total carnitine acetyltransferase activity (mitochondrial and peroxisomal) and peroxisomal beta-oxidation were markedly increased at both dose levels in all strains examined. Cytosolic glutathione peroxidase activity, measured using both t-butylhydroperoxide and hydrogen peroxide as substrates, was decreased on treatment to approximately 50% of the control value. In treated animals, a marked increase in mRNA levels coding for cytochrome P-450 IVA1 and the peroxisomal bifunctional protein of the fatty acid beta-oxidation spiral was observed. However, mRNA levels coding for glutathione peroxidase appeared unchanged following ciprofibrate administration, in contrast to the above-noted decrease of glutathione peroxidase enzyme activity. Taken collectively, our results have further substantiated a close association between the induction of microsomal cytochrome P-450 IVA1, peroxisomal beta-oxidation and total carnitine acetyltransferase activity in rat liver, and have performed a conceptual basis for the rationalization of the chronic toxicity of peroxisome proliferators in this species.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1083-93
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:2390105-Administration, Oral, pubmed-meshheading:2390105-Animals, pubmed-meshheading:2390105-Body Weight, pubmed-meshheading:2390105-Cell Division, pubmed-meshheading:2390105-Clofibrate, pubmed-meshheading:2390105-Clofibric Acid, pubmed-meshheading:2390105-Cytochrome P-450 CYP1A1, pubmed-meshheading:2390105-Cytochrome P-450 Enzyme System, pubmed-meshheading:2390105-Fibric Acids, pubmed-meshheading:2390105-Glutathione Peroxidase, pubmed-meshheading:2390105-Hypolipidemic Agents, pubmed-meshheading:2390105-Male, pubmed-meshheading:2390105-Microbodies, pubmed-meshheading:2390105-Microsomes, Liver, pubmed-meshheading:2390105-Organ Size, pubmed-meshheading:2390105-Oxidoreductases, pubmed-meshheading:2390105-Oxidoreductases, N-Demethylating, pubmed-meshheading:2390105-Rats, pubmed-meshheading:2390105-Rats, Gunn, pubmed-meshheading:2390105-Rats, Inbred F344, pubmed-meshheading:2390105-Rats, Inbred Strains, pubmed-meshheading:2390105-Species Specificity
pubmed:year
1990
pubmed:articleTitle
Characterization of the hepatic responses to the short-term administration of ciprofibrate in several rat strain. Co-induction of microsomal cytochrome P-450 IVA1 and peroxisome proliferation.
pubmed:affiliation
University of Surrey, Department of Biochemistry, Molecular Toxicology Group, Guildford, U.K.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't