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

被引:0
作者
Shattuck, KE
Grinnell, CD
Goldman, AS
Rassin, DK
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关键词
TNF-alpha; amino acids; glutathione; isolated rat liver;
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R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: TNF-alpha mediates the hepatic response to sepsis by mechanisms which are not well understood, TNF-alpha is known to stimulate the hepatocellular uptake of specific amino acids in vivo; however, little is known about the direct effects of TNF-alpha 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-alpha on the secretion of amino acids and glutathione into bile and perfusate. Livers taken from adult male Sprague-Dawley rats were perfused with TNF-alpha at a dose of 1 or 2 mu g. Bile and perfusate were collected for the quantitation of amino acid and glutathione concentrations. Results: Administration of 2 mu g TNF-alpha resulted in significant increases in biliary and perfusate concentrations of branched chain, gluconeogenic, and total amino acids, TNF-alpha was also associated with dose-related increases in oxygen uptake, and greater biliary concentrations of glutathione. Conclusion: TNF-alpha has direct effects upon hepatic amino acid metabolism, which represent some of the early events involved in the mechanism of response to sepsis.
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页码:64 / 69
页数:6
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