Apparent induction of microsomal carboxylesterase activities in tissues of clofibrate-fed mice and rats.
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.
D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis*; D002994:Clofibrate / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008294:Malathion / Q000494:pharmacology; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009596:Nitrophenols / Q000494:pharmacology; D010795:Phthalic Acids / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000201:enzymology
D009596:Nitrophenols; D010795:Phthalic Acids; D013386:Succinates; C008642:4-nitrophenyl acetate; D002265:Carboxylic Ester Hydrolases; C052819:diethyl succinate; D002994:Clofibrate; D008294:Malathion; C007379:diethyl phthalate