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Related Experiment Videos

Decrease in the hepatic clearance of hepatocyte growth factor in carbon tetrachloride-intoxicated rats

K X Liu1, Y Kato, M Yamazaki

  • 1Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

Hepatology (Baltimore, Md.)
|April 1, 1993
PubMed
Summary
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Decreased liver uptake of hepatocyte growth factor (HGF) in rats with liver injury significantly reduces its clearance. This impaired hepatic clearance of HGF may contribute to elevated circulating HGF levels observed in liver diseases.

Area of Science:

  • Hepatology
  • Biochemistry
  • Pharmacokinetics

Background:

  • Elevated plasma hepatocyte growth factor (HGF) levels are observed in various liver diseases.
  • The mechanisms contributing to increased circulating HGF, specifically hepatic handling, require further elucidation.

Purpose of the Study:

  • To investigate whether reduced hepatic uptake or clearance of HGF contributes to elevated plasma HGF levels.
  • To kinetically analyze hepatic HGF handling in a rat model of carbon tetrachloride-induced liver injury.

Main Methods:

  • In vivo and ex vivo (perfused liver) kinetic analysis of tracer 125I-HGF in rats.
  • Determination of tissue and plasma clearance rates of HGF.
  • Assessment of cell-surface-bound and internalized HGF following liver perfusion.

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Main Results:

  • Liver and adrenal clearance of HGF significantly decreased in carbon tetrachloride-treated rats.
  • Hepatic clearance, explaining the majority of total body clearance, was reduced to approximately 40% of control values at 24 hours post-injury.
  • Both internalized and cell-surface-bound HGF significantly decreased, suggesting impaired receptor-mediated endocytosis.

Conclusions:

  • Reduced hepatic clearance of HGF, primarily due to impaired receptor-mediated endocytosis, is a key factor in elevated circulating HGF levels during liver injury.
  • The findings suggest that decreased hepatic HGF uptake and clearance contribute to the pathophysiology of liver diseases.