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© 1994 Oxford University Press

research-article

Chlordecone Pretreatment Alters [14C]Chlordecone and [14C]Cholesterol Transport Kinetics in the Perfused Rat Liver1,2

DUNCAN J. GILROY, HILLARY M. CARPENTER and LAWRENCE R. CURTIS3

Oak Creek Laboratorty of Biology, Department of Fisheries and Wildlife 104 Nash Hall Oregon State University Corvallis, Oregon 97331

Received May 10, 1993; accepted October 4, 1993

Previous work demonstrated that pretreatment of mice with low doses of the organochlorine insecticide chlordecone (CD) altered the tissue disposition of a subsequent [14C]CD or [14C]- cholesterol challenge dose. The profile of these changes was consistent with the induction of a protein integral to hepatic CD/cholesterol turnover. The present study was undertaken to confirm similar in vivo effects in the rat and to analyze potential CD-induced changes in hepatic transport kinetics in the per fused rat liver. For in vivo experiments, male, Sprague-Dawley rats were treated with CD (5, 15, or 40 mg/kg) and challenged 3 or 7 days later with a 5 mg/kg [14C]CD tracer dose. Rats challenged 3 days after treatment and evaluated 16 hr later showed a dose-dependent decrease in hepatic [14C]CD relative to controls. This decrease could not be attributed to alterations in liver mass or total liver lipid. For kinetics studies, rats received 15 mg/kg CD and livers were perfused 3 days later. Following a brief (5–7 min) single-pass perfusion, the perfusate was replaced with recirculating buffer containing albumin-bound [3H]oleic acid or high-density lipoprotein-bound [14C]CD or [14C]cholesterol Livers from pretreated animals had significantly decreased rates of [14C]CD and [14C]cholesterol uptake. Efflux of [14C]CD and biliary excretion of [14C] were increased. No changes were observed in uptake or biliary excretion of [3H]oleic acid. SDS-PAGE of hepatic cytosol revealed an enhanced band in tensity corresponding to a Mr of 25,600 in livers from pretreated rats. These results are supportive of a competitive interaction between cholesterol and CD for proteins associated with hepa tocellular transport and excretion and suggest that CD pretreatment may have an inductive effect on these proteins.


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