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Journal of Cancer Research and Clinical Oncology

, Volume 114, Issue 4, pp 341–346 | Cite as

Time-dependence and differential induction of rat and guinea pig peroxisomalβ-oxidation, palmitoyl-CoA hydrolase, cytosolic and microsomal epoxide hydrolase after treatment with hypolipidemic drugs

  • F. Oesch
  • R. Hartmann
  • Ch. Timms
  • M. Strolin-Benedetti
  • P. Dostert
  • W. Wörner
  • L. Schladt
Original Papers Experimental Oncology

Summary

Fischer-344 rats and Hartley guinea pigs received a diet containing 0.01 % (w/w), 0.05% (w/w), or 0.25% (w/w) of the hypolipidemic drug fenofibrate. Rats were treated for 4, 7, 14, or 21 days, and a clear dose-dependent and weak time-dependent increase in liver/body weight ratio was observed. The specific activity of peroxisomalβ-oxidation increased linearly with time at all concentrations used. A dose-dependent increase in cEH was observed, but the activity remained constant after treatment for 7 days. Enhancement of palmitoyl-CoA hydrolase was dose-dependent, but was similar at all 4 time points investigated. In contrast to the other enzyme activities, mEH was not or only minimally (< 1.5-fold) induced. In contrast to the rat, treatment of guinea pigs with fenofibrate for 1 week did not change liver weight or enzyme activities. Prolonged treatment of guinea pigs (4 weeks) with fenofibrate did not result in an increase in enzyme activities. This was also observed with clofibrate whereas tiadenol caused a slight increase in enzyme activities (1.5- to 2.6-fold). In contrast to the guinea pig each of the three hypolipidemic drugs led to an increase in enzyme activities in the rat liver after treatment for 1 week.

Key words

Cytosolic epoxide hydrolase Microsomal epoxide hydrolase Peroxisomalβ-oxidation Peroxisome proliferators Species differences 

Abbreviations

STO

2-phenyloxirane (styrene 7,8-oxide)

TSO

trans-2,3-diphenyloxirane (trans-stilbene oxide)

mEH

microsomal epoxide hydrolase with broad substrate specificity for various xenobiotic epoxides, specifically including benzo(a)-pyrene 4,5-oxide

cEH

cytosolic epoxide hydrolase; DEHP, di-(2-ethylhexyl)phthalate

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • F. Oesch
    • 1
  • R. Hartmann
    • 1
  • Ch. Timms
    • 1
  • M. Strolin-Benedetti
    • 2
  • P. Dostert
    • 2
  • W. Wörner
    • 1
  • L. Schladt
    • 1
  1. 1.Institut für Toxikologie der Universität MainzMainzGermany
  2. 2.Laboratories FournierCentre de RecherchesFontaine lès DijonFrance

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