Chlordecone Pretreatment Alters [14C]Chlordecone and [14C]Cholesterol Transport Kinetics in the Perfused Rat Liver
| Autor: | Lawrence R. Curtis, Hillary M. Carpenter, Duncan J. Gilroy |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Lipoproteins Oleic Acids 7-Alkoxycoumarin O-Dealkylase In Vitro Techniques Toxicology Rats Sprague-Dawley Excretion chemistry.chemical_compound Cytosol Cytochrome P-450 Enzyme System In vivo Albumins Internal medicine Cytochrome P-450 CYP1A1 medicine Animals Bile Tissue Distribution Chemistry Cholesterol Organ Size Lipid Metabolism Rats Oleic acid Endocrinology Liver Mechanism of action Chlordecone Enzyme Induction Electrophoresis Polyacrylamide Gel Efflux medicine.symptom Oxidoreductases Perfusion |
| Zdroj: | Fundamental and Applied Toxicology. 22:286-292 |
| ISSN: | 0272-0590 |
| DOI: | 10.1006/faat.1994.1032 |
| Popis: | Chlordecone Pretreatment Alter [14C]Chlordecone and [14C]Cholesterol Transport Kinetics in the Perfused Rat Liver. Gilroy, D. J., Carpenter, H. M., and Curtis, L. R. (1994). Fundam. Appl. Toxicol. 22, 286-292. 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 perfused 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]cholesterol were increased. No changes were observed in uptake or biliary excretion of [3H]oleic acid. SDS-PAGE of hepatic cytosol revealed an enhanced band intensity corresponding to a Mr of 25,600 in livers from pretreated rat. These results are supportive of a competitive interaction between cholesterol and CD for proteins associated with hepatocellular transport and excretion and suggest that CD pretreatment may have an inductive effect on these proteins. |
| Databáze: | OpenAIRE |
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