+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Comparative induction of cytochrome P450IVA1 and peroxisome proliferation by ciprofibrate in the rat and marmoset

Comparative induction of cytochrome P450IVA1 and peroxisome proliferation by ciprofibrate in the rat and marmoset

Archives of Toxicology 65(2): 106-113

Chronic ciprofibrate administration resulted in distinct differences in hepatic responses between the two species examined. In the rat, hepatomegaly was observed with the coordinate induction of carnitine acetyltransferase, peroxisomal beta-oxidation and cytochrome P450IVA1 activities. The latter induction of cytochrome P450IVA1-dependent fatty acid hydroxylase activity was specific to this cytochrome P450 sub family, as ciprofibrate pretreatment resulted in an inhibition of the enzyme activities associated with the cytochrome P450 IIB and IA sub-families. Induction of mitochondrial enzymes were also noted in the rat, but at a substantially lower level than the microsomal and peroxisomal enzyme changes noted above. The majority of these enzyme changes were reversible in the rat after a 4-week, inducer-free period. In contrast, the marmoset displayed a different pattern of enzyme changes in response to ciprofibrate and at the high dose level, inhibition of microsomal fatty acid hydroxylase activity was observed in addition to no change in carnitine acetyltransferase activity. Although peroxisomal beta-oxidation activity was induced in the marmoset, the specific activity was 10-fold lower than in the rat, concomitant with only minimum changes in the liver: body weight ratio. Taken collectively, our data have demonstrated that the marmoset is relatively refractory to ciprofibrate-induced liver enzyme changes with the implication that the extrapolation of the associated hepatotoxicity clearly documented in rodents must be viewed with extreme caution in non-human primates.

(PDF emailed within 0-6 h: $19.90)

Accession: 039619245

Download citation: RISBibTeXText

PMID: 1905530

DOI: 10.1007/bf02034935

Related references

Stereochemical induction of cytochrome P450IVA1 (P452) and peroxisome proliferation in male rat. Advances in Experimental Medicine and Biology 283: 267-270, 1991

On the mechanism of induction of microsomal cytochrome P450IVA1 and peroxisome proliferation in rat liver by clofibrate. Biochemical Pharmacology 40(12): 2727-2732, 1990

Stereochemical selectivity in the induction of cytochrome P450IVA1 (P452)-dependent fatty acid hydroxylation and peroxisome proliferation. Biochemical Pharmacology 41(5): 769-774, 1991

Species differences in ciprofibrate induction of hepatic cytochrome P-450 4A1 and peroxisome proliferation. Journal of Biochemical Toxicology 7(3): 183-191, 1992

Characterization of the hepatic responses to the short term administration of ciprofibrate in several rat strains co induction of microsomal cytochrome p 450 iva1 and peroxisome proliferation. Biochemical Pharmacology 40(5): 1083-1094, 1990

Lack of peroxisome proliferation in marmoset liver following treatment with ciprofibrate for 3 years. Fundamental & Applied Toxicology. 22(1): 58-64, 1994

Induction of acyl-CoA oxidase and cytochrome P450IVA1 RNA in rat primary hepatocyte culture by peroxisome proliferators. Biochemical Journal 280: 249-253, 1991

Induction of peroxisome proliferation in rainbow trout exposed to ciprofibrate. Toxicology & Applied Pharmacology 104(3): 476-482, 1990

Induction of peroxisome proliferation and hepatic tumors in c57bl 6n mice by ciprofibrate a hypolipidemic compound. British Journal of Cancer 58(1): 46-51, 1988

Induction by ciprofibrate of hepatic peroxisome proliferation in rats pigeons chickens cats and rhesus monkeys. Federation Proceedings 41(5): ABSTRACT 8601, 1982

Tissue specificity in the induction of peroxisome proliferation associated polypeptide ppa 80 and peroxisomal beta oxidation in rats by ciprofibrate. Federation Proceedings 44(3): 663, 1985

Influence of purified diets on the induction of cell proliferation by the hepatic tumor promoters 2,2,4,4,5,5-hexachlorobiphenyl and the peroxisome proliferator ciprofibrate. FASEB Journal 17(4-5): Abstract No 711 15, March, 2003