Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy.
The content of the tryptophan metabolites quinolinic acid (QUIN), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) was measured in various brain areas of rats bearing a portocaval anastomosis (PCA) for 4 weeks, using mass fragmentography or HPLC. In these animals, the content of the excitotoxic compound QUIN increased by 75% in the cortex and 125% in the cerebellum. The content of 5-HT increased by 27% in the brainstem. No changes occurred in other brain areas. On the other hand, the content of 5-HIAA increased by 66% in the cortex, 65% in the caudate, 64% in the hippocampus, 120% in the diencephalon, and 185% in the brainstem. Probenecid administration caused a larger increase of 5-HIAA accumulation in various brain areas of PCA-bearing rats than in those of sham-operated controls. The cortical content of QUIN and 5-HIAA increased after administration of ammonium acetate (7 mmol/kg), whereas an equimolar amount of sodium acetate was inactive. These results confirm that profound changes in the disposition of tryptophan occur in the brains of experimental animals used as models of hepatic encephalopathy. Furthermore, this study adds the excitotoxic compound QUIN to the list of molecules possibly involved in the pathogenesis of this brain disorder.
F
F
Moroni
G
G
Lombardi
V
V
Carlà
D
D
Pellegrini
G L
GL
Carassale
C
C
Cortesini
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D011167:Portacaval Shunt, Surgical; D011339:Probenecid / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
D000085:Acetates; D011725:Pyridines; D011805:Quinolinic Acids; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D017378:Quinolinic Acid; D011339:Probenecid; C018824:ammonium acetate