Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver

Mette Lund, Leslie Kang, Niels Tygstrup, Allan W. Wolkoff, Peter Ott

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) initiates cholestasis. Whether this process is mediated by tumor necrosis factor-α (TNF-α) and whether the cholestatic response to LPS is associated with intrahepatic accumulation of possibly toxic substances are under debate. To study these questions the hepatic uptake and biliary excretion of indocyanine green (ICG) was examined in the isolated perfused rat liver 18 h after intravenous treatment of rats with either saline, 1 mg/kg body wt LPS, or LPS and intraperitoneal pentoxifylline (POF) (n = 6 in each group). POF inhibits TNF-α release after LPS administration. LPS induced a typical acute-phase response with increased mRNA for acute-phase proteins, reduced albumin mRNA, and increased hepatic uptake of alanine. Intrinsic hepatic clearance of ICG in controls (1.01 ± 0.05 ml · min-1 · g liver-1) was similarly decreased by LPS alone (0.62 ± 0.04 ml · min-1 · g-1; P = 0.002 vs. control) or combined with POF (0.66 ± 0.06 ml · min-1 · g-1). A kinetic analysis indicated that LPS reduced both uptake and excretion processes in a balanced manner, so that intrahepatic ICG content was unaffected or even slightly reduced, as confirmed by measurement of ICG contents in the perfused livers. In livers from parallel-treated nonperfused rats, mRNA for the organic anion transporting protein-1 (Oatp1, which is likely to mediate ICG uptake) was unaffected by LPS, whereas the concentration of Oatp1 protein was reduced. Thus LPS induced an acute-phase response that included downregulation of ICG uptake by reduction of Oatp1 protein concentration, possibly at a posttranscriptional level. TNF-α, appears not to be the mediator because POF did not modify these LPS effects.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume277
Issue number1 40-1
StatePublished - Jul 1999

Fingerprint

Indocyanine Green
Alanine
Lipopolysaccharides
Liver
Pentoxifylline
Acute-Phase Reaction
Tumor Necrosis Factor-alpha
Messenger RNA
Proteins
Acute-Phase Proteins
Poisons
Cholestasis
Anions
Albumins
Down-Regulation

Keywords

  • Acute-phase response
  • Cytokines
  • Endotoxin
  • Lipopolysaccharide
  • Oatp1
  • Tumor necrosis factor- α

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver. / Lund, Mette; Kang, Leslie; Tygstrup, Niels; Wolkoff, Allan W.; Ott, Peter.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 277, No. 1 40-1, 07.1999.

Research output: Contribution to journalArticle

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abstract = "Lipopolysaccharide (LPS) initiates cholestasis. Whether this process is mediated by tumor necrosis factor-α (TNF-α) and whether the cholestatic response to LPS is associated with intrahepatic accumulation of possibly toxic substances are under debate. To study these questions the hepatic uptake and biliary excretion of indocyanine green (ICG) was examined in the isolated perfused rat liver 18 h after intravenous treatment of rats with either saline, 1 mg/kg body wt LPS, or LPS and intraperitoneal pentoxifylline (POF) (n = 6 in each group). POF inhibits TNF-α release after LPS administration. LPS induced a typical acute-phase response with increased mRNA for acute-phase proteins, reduced albumin mRNA, and increased hepatic uptake of alanine. Intrinsic hepatic clearance of ICG in controls (1.01 ± 0.05 ml · min-1 · g liver-1) was similarly decreased by LPS alone (0.62 ± 0.04 ml · min-1 · g-1; P = 0.002 vs. control) or combined with POF (0.66 ± 0.06 ml · min-1 · g-1). A kinetic analysis indicated that LPS reduced both uptake and excretion processes in a balanced manner, so that intrahepatic ICG content was unaffected or even slightly reduced, as confirmed by measurement of ICG contents in the perfused livers. In livers from parallel-treated nonperfused rats, mRNA for the organic anion transporting protein-1 (Oatp1, which is likely to mediate ICG uptake) was unaffected by LPS, whereas the concentration of Oatp1 protein was reduced. Thus LPS induced an acute-phase response that included downregulation of ICG uptake by reduction of Oatp1 protein concentration, possibly at a posttranscriptional level. TNF-α, appears not to be the mediator because POF did not modify these LPS effects.",
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