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This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/G93    most recent 00196.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Hung, D. Y. Articles by Roberts, M. S. Search for Related Content PubMed PubMed Citation Articles by Hung, D. Y. Articles by Roberts, M. S.

LIVER AND BILIARY TRACT

Reduced hepatic extraction of palmitate in steatosis correlated to lower level of liver fatty acid binding protein

¹Department of Medicine, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Queensland, Australia; and ²Faculty of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 28 April 2004 ; accepted in final form 30 August 2004

Nonalcoholic fatty liver disease is the most common of all liver diseases. The hepatic disposition [³H]palmitate and its low-molecular-weight metabolites in perfused normal and steatotic rat liver were studied using the multiple indicator dilution technique and a physiologically based slow diffusion/bound pharmacokinetic model. The steatotic rat model was established by administration of 17-ethynylestradiol to female Wistar rats. Serum biochemistry markers and histology of treated and normal animals were assessed and indicated the presence of steatosis in the treatment group. The steatotic group showed a significantly higher alanine aminotransferase-to-aspartate aminotransferase ratio, lower levels of liver fatty acid binding protein and cytochrome P-450, as well as microvesicular steatosis with an enlargement of sinusoidal space. Hepatic extraction for unchanged [³H]palmitate and production of low-molecular-weight metabolites were found to be significantly decreased in steatotic animals. Pharmacokinetic analysis suggested that the reduced extraction and sequestration for palmitate and its metabolites was mainly attributed to a reduction in liver fatty acid binding protein in steatosis.

17-ethynylestradiol; hepatic palmitate disposition

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