The acute effects of TNF-α on the isolated perfused rat liver

Karen E. Shattuck, Chali D. Grinnell, Armond S. Goldman, David K. Rassin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: TNF-α mediates the hepatic response to sepsis by mechanisms which are not well understood. TNF-α is known to stimulate the hepatocellular uptake of specific amino acids in vivo; however, little is known about the direct effects of TNF-α on hepatic amino acid or glutathione homeostasis, which is a potential factor in the acute hepatic response to sepsis. Methods: Using the isolated perfused rat liver, we characterized the effects of TNF-α on the secretion of amino acids and glutathione into bile and perfusate. Livers taken from adult male Sprague-Dawley rats were perfused with TNF-α at a dose of 1 or 2 μg. Bile and perfusate were collected for the quantitation of amino acid and glutathione concentrations. Results: Administration of 2 αg TNF-α resulted in significant increases in biliary and perfusate concentrations of branched chain, gluconeogenic, and total amino acids. TNF-α was also associated with dose-related increases in oxygen uptake, and greater biliary concentrations of glutathione. Conclusion: TNF-α has direct effects upon hepatic amino acid metabolism, which represent some of the early events involved in the mechanism of response to sepsis.

Original languageEnglish (US)
Pages (from-to)64-69
Number of pages6
JournalJournal of Investigative Medicine
Issue number2
StatePublished - 1996


  • Amino acids
  • Glu tathione
  • Isolated rat liver
  • TNF-α

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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