Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1995-1-26
pubmed:abstractText
The objective of this study was to compare the effects of perfluorodecanoic acid (PFDA) and ciprofibrate on the induction of hepatic toxicity and on hepatocellular proliferation in rats. In the first study, rats were first subjected to partial hepatectomy and then injected with [3H]thymidine (20 microCi/injection) at 23, 24, 25, 47, 48 and 49 h afterwards. After a 2 week recovery period, rats were injected with one of four levels of PFDA (0.3, 1.0, 3.0 or 10 mg/kg/injection) in four i.p. doses every 14 days, or were fed 0.01% or 0.003% ciprofibrate. Six days after the last PFDA injection and three days before the animals were killed, an osmotic minipump containing 20 mg/ml 5-bromo-2'-deoxyuridine (BrdU) was implanted s.c. for the measurement of DNA synthesis. Peroxisomal fatty acyl-CoA oxidase activity was significantly enhanced in both PFDA and ciprofibrate-treated groups in a dose-dependent manner. Hepatotoxicity, measured as the loss of [3H]thymidine from hepatic DNA, was not significantly affected by any of the treatments. Hepatic DNA synthesis was significantly increased only in rats receiving the highest dose of PFDA. In order to determine the time course of ciprofibrate- and PFDA-induced cell proliferation, we conducted another study with more time points. Rats were fed 0.01% ciprofibrate or were injected every 14 days with 3 or 10 mg PFDA/kg body weight for 10 days, 24 days, 6 weeks, 26 weeks or 54 weeks. Cell proliferation was quantified as in the first study. Ciprofibrate increased cell proliferation at the early but not the later time points, whereas PFDA increased cell proliferation at most times throughout the study. This study demonstrates that PFDA and ciprofibrate do not selectively induce hepatic toxicity and that their effects on cell proliferation do not correlate with their carcinogenic or promoting activities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2847-50
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Effect of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on hepatic cell proliferation and toxicity in Sprague-Dawley rats.
pubmed:affiliation
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't