Apparent induction of microsomal carboxylesterase activities in tissues of clofibrate-fed mice and rats

Toxicol Appl Pharmacol. 1987 Jul;89(3):361-9. doi: 10.1016/0041-008x(87)90155-4.


Treatment with 0.5% (w/w) dietary clofibrate, a peroxisome proliferator, for 14 days induced microsomal carboxylesterase activities for five substrates including malathion, clofibrate, diethylsuccinate, diethylphthalate, and p-nitrophenylacetate in liver and kidney of male Swiss-Webster mice and Sprague-Dawley rats. The induction was substrate, tissue, and species dependent. The carboxylesterase activity was induced in mouse from 1.2- to 2.2-fold (liver) and from 1.1- to 1.7-fold (kidney) depending upon substrate used. Analogous values from rat ranged from 1.0- to 1.4-fold (liver) and from 1.1- to 1.8-fold (kidney). Enzyme activities were either decreased or not affected in testes of treated mice and rats. Substituted trifluoroketones ("transition-state" inhibitors of carboxylesterase) were found to be very potent inhibitors of clofibrate-metabolizing carboxylesterase(s) and to be potentially useful in distinguishing among isozymes. The inhibition data suggested that changes in carboxylesterase activity following clofibrate treatment were both qualitative and quantitative.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carboxylic Ester Hydrolases / biosynthesis*
  • Clofibrate / pharmacology*
  • Enzyme Induction / drug effects
  • Kidney / drug effects
  • Kidney / enzymology
  • Malathion / pharmacology
  • Male
  • Mice
  • Microsomes / drug effects*
  • Microsomes / enzymology
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Nitrophenols / pharmacology
  • Phthalic Acids / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Succinates / pharmacology
  • Testis / drug effects
  • Testis / enzymology


  • Nitrophenols
  • Phthalic Acids
  • Succinates
  • 4-nitrophenyl acetate
  • Carboxylic Ester Hydrolases
  • diethyl succinate
  • Clofibrate
  • Malathion
  • diethyl phthalate