Selective induction of bilirubin UDP-glucuronosyl-transferase by perfluorodecanoic acid.
Differential effects of perfluorodecanoic acid (PFDA) on rat liver UDP-glucuronosyltransferase isoenzymes have been observed after a single i.p. administration of the compound to young male Sprague-Dawley rats. (1) Bilirubin glucuronidation was induced 2-fold. The induced state was stable for at least 3 weeks. (2) Glucuronidation of 1-naphthol, morphine and testosterone was decreased to half of the control values. These decreases were maximal after 12 days but all three activities returned to normal levels after 3 weeks. (3) Immunoblotting experiments indicated that the differential effects of PFDA on UDP-glucuronosyltransferase activities were due to modulation of enzyme protein concentrations rather than activation/inactivation mechanisms. With respect to its influence on UDP-glucuronosyltransferase isoenzymes, PFDA may be classified as a clofibrate-type inducer. The persistence of the induction after a single application however is unique among peroxisome proliferators and therefore PFDA may be a useful, elective inducer of bilirubin glucuronidation.
Arand
M
M
Institute of Toxicology, University of Mainz, F.R.G.
Coughtrie
M W
MW
Burchell
B
B
Oesch
F
F
Robertson
L W
LW
D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005466:Fluorocarbons / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000032:analysis / Q000096:biosynthesis*; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003652:Decanoic Acids; D005466:Fluorocarbons; D007527:Isoenzymes; C036567:perfluorodecanoic acid; D014453:Glucuronosyltransferase