Role of tryptophan in the elevated serotonin-turnover in hepatic encephalopathy.
The increase of the brain levels of 5-hydroxyindoleacetic acid (5-HIAA) in hepatic encephalopathy (HE) suggests an increased turnover of serotonin (5-HT). To study the role of tryptophan on the increased brain 5-HT metabolism in HE, we attempted to monitor brain levels of tryptophan in rats with thioacetamide-induced acute liver failure by intravenous infusion of branched-chain amino acids (BCAA). The effect of this treatment on 5-HT synthesis and metabolism was investigated in five brain areas. BCAA-infusions (1 and 2 gm/kg/24 h) increased the ratio BCAA/aromatic amino acids in plasma two- and fourfold, respectively, and lowered both plasma and brain levels of tryptophan. At the higher BCAA-dose all parameters suggesting an altered brain 5-HT metabolism (increased brain levels of 5-HT and 5-HIAA, increased 5-HIAA/5-HT ratio) were almost completely normalized. These results provide further evidence for the role of tryptophan in the elevation of brain 5-HT metabolism and for a potential role of BCAA in the treatment of HE.
Herneth
A M
AM
Department of Internal Medicine IV, Gastroenterology and Hepatology, University of Vienna, Austria.
Steindl
P
P
Ferenci
P
P
Roth
E
E
Hörtnagl
H
H
D000596:Amino Acids / Q000097:blood; D000597:Amino Acids, Branched-Chain / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism / Q000502:physiology*
D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan