Plasma and brain levels of oxindole in experimental chronic hepatic encephalopathy: effects of systemic ammonium acetate and L-tryptophan.
It has previously been shown that the neurodepressant L-tryptophan metabolite oxindole is increased in the blood and brain of rats with fulminant hepatic failure and in the blood of cirrhotic patients affected by chronic hepatic encephalopathy. In the present investigation, we found that oxindole levels were significantly increased in the blood and brain of portacaval-shunted rats, an animal model of chronic hepatic encephalopathy, compared with sham-operated controls. A further increase in plasma and brain oxindole content was found after oral administration of L-tryptophan (300 mg/kg) to both portacaval-shunted or sham-operated animals, while intraperitoneal injection of the amino acid did not modify oxindole content either in brain or blood. Ammonium acetate administration (4.0 mmol/kg, intraperitoneal) reversibly deteriorated the neurological status of portacaval-shunted animals, but did not modify, in a directly related manner, plasma and brain oxindole content. The present findings are in line with the possibility that oxindole may be an additional L-tryptophan-related candidate in the pathogenesis of chronic hepatic encephalopathy.
Bergqvist
P B
PB
Department of Clinical Pharmacology, Lund University, Sweden.
Carpenedo
R
R
Apelqvist
G
G
Moroni
F
F
Bengtsson
F
F
D000085:Acetates / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000209:etiology; D007211:Indoles / Q000097:blood*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D008297:Male; D000078183:Oxindoles; D011167:Portacaval Shunt, Surgical; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000494:pharmacology*
D000085:Acetates; D007211:Indoles; D000078183:Oxindoles; C022960:2-oxindole; D014364:Tryptophan; C018824:ammonium acetate