Archives of Toxicology

, Volume 69, Issue 7, pp 491–497 | Cite as

Altered hepatic eicosanoid concentrations in rats treated with the peroxisome proliferators ciprofibrate and perfluorodecanoic acid

  • Mary W. Wilson
  • L. Travis Lay
  • Ching K. Chow
  • Hsin -Hsiung Tai
  • Larry W. Robertson
  • Howard P. Glauert
Original Investigation

Abstract

Several hypolipidemic drugs, plasticizers, and other chemicals induce hepatic peroxisome proliferation and hepatocellular carcinomas in rodents. These agents induce and promote hepatocarcinogenesis by unknown mechanisms, since most studies have not found them to be genotoxic. Peroxisome proliferators increase the expression of several genes, including those for the enzymes of the peroxisomal β-oxidation path-way and the cytochrome P-450 4A family, which metabolize lipids, including eicosanoids and their precursor fatty acids. The peroxisome proliferators ciprofibrate and perfluorodecanoic acid (PFDA) were therefore examined for their ability to alter hepatic eicosanoid concentrations. Rats received injections of 3 or 10 mg PFDA/kg body weight every 14 days or were fed 0.01% ciprofibrate for 10 days, 24 days, 6 weeks, 26 weeks, or 54 weeks. The activity of the peroxisomal enzyme fatty acyl CoA oxidase was significantly increased by both ciprofibrate and PFDA at all times. Hepatic concentrations of prostaglandins E2 and F (PGE2, PGF) thromboxane B2 (TXB2), and leukotriene C4 (LTC4) were measured by immunoassay. Concentrations of PGE2, PGF, and TXB2 were decreased in livers of rats receiving ciprofibrate or PFDA compared to livers of control rats, with ciprofibrate exerting a greater effect than PFDA at the doses used. Hepatic LTC4 concentrations were significantly increased by ciprofibrate at 10 days and PFDA at 54 weeks, and significantly decreased by PFDA at 26 weeks. These alterations in eicosanoid concentrations may be important in the natural history of peroxisome proliferator-induced hepatocarcinogenesis.

Key words

Ciprofibrate Perfluorodecanoic acid Eicosanoids Peroxisome 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Mary W. Wilson
    • 1
  • L. Travis Lay
    • 1
  • Ching K. Chow
    • 1
    • 2
  • Hsin -Hsiung Tai
    • 3
  • Larry W. Robertson
    • 2
  • Howard P. Glauert
    • 1
    • 2
  1. 1.Department of Nutrition and Food ScienceUniversity of KentuckyLexingtonUSA
  2. 2.Graduate Center for ToxicologyUniversity of KentuckyLexingtonUSA
  3. 3.College of PharmacyUniversity of KentuckyLexingtonUSA

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