Chlordecone altered hepatic disposition of [{sup 14}C]cholesterol and plasma cholesterol distribution but not SR-BI or ABCG8 proteins in livers of C57BL/6 mice

Journal Article · Sun Jun 15 04:00:00 EDT 2008 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2008.01.023· OSTI ID:21140860

Lee, Junga; Scheri, Richard C ^[1]

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1. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States)

Organochlorine (OC) insecticides continue to occur in tissues of humans and wildlife throughout the world although they were banned in the United States a few decades ago. Low doses of the OC insecticide chlordecone (CD) alter hepatic disposition of lipophilic xenobiotics and perturb lipid homeostasis in rainbow trout, mice and rats. CD pretreatment altered tissue and hepatic subcellular distribution of exogenous [{sup 14}C]cholesterol (CH) equivalents 4 and 16 h after a bolus intraperitoneal (ip) injection of 5 ml corn oil/kg that contained 10 mg CH/kg. CD pretreatment altered tissue distribution of exogenously administered [{sup 14}C]CH by decreased hepatic and renal accumulation, and increased biliary excretion up to 300%. Biliary excretion of polar [{sup 14}C]CH metabolites was not altered by CD. CD pretreatment decreased subcellular distribution of [{sup 14}C]CH equivalents in hepatic cytosol and microsomes and lipoprotein-rich fraction-to-homogenate ratio. CD pretreatment increased the ratio of [{sup 14}C]CH equivalents in high density lipoprotein (HDL) to that in plasma and reduced [{sup 14}C]CH equivalents in the non-HDL fraction 4 h after a bolus lipid dose. CD pretreatment increased plasma non-HDL total CH by 80% 4 h after a bolus lipid dose. Scavenger receptor class B type I (SR-BI) and ATP-binding cassette transporter G8 (ABCG8) proteins were quantified by western blotting in hepatic membranes from control and CD treated mice. Liver membrane contents of SR-BI and ABCG8 proteins were unchanged by CD pretreatment. The data demonstrated that a single dose of CD altered CH homeostasis and lipoprotein metabolism.

• OSTI ID: 21140860
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 229; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBON 14
CHOLESTEROL
CORN OIL
DOSES
EXCRETION
HOMEOSTASIS
INSECTICIDES
KIDNEYS
LIPOPROTEINS
LIVER
METABOLISM
METABOLITES
MICE
ORGANIC CHLORINE COMPOUNDS
RATS
RECEPTORS
SUBCELLULAR DISTRIBUTION
TISSUE DISTRIBUTION
TROUT