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The relationship between plasma and brain quinolinic acid levels and the severity of hepatic encephalopathy in animal models of fulminant hepatic failure.

Abstract：

:Quinolinic acid is an excitatory, neurotoxic tryptophan metabolite proposed to play a role in the pathogenesis of hepatic encephalopathy. This involvement was investigated in rat and rabbit models of fulminant hepatic failure at different stages of hepatic encephalopathy. Although plasma and brain tryptophan levels were significantly increased in all stages of hepatic encephalopathy, quinolinic acid levels increased three-to sevenfold only in the plasma, CSF, and brain regions of animals in stage IV hepatic encephalopathy. Plasma-CSF and plasma-brain quinolinic acid levels in rats and rabbits with fulminant hepatic failure were strongly correlated, with CSF and brain concentrations approximately 10% those of plasma levels. Moreover, there was no significant regional difference in brain quinolinic acid concentrations in either model. Extrahepatic indoleamine-2,3-dioxygenase activity was not altered in rats in stage IV hepatic encephalopathy, but hepatic L-tryptophan-2,3-dioxygenase activity was increased. These results suggest that quinolinic acid synthesized in the liver enters the plasma and then accumulates in the CNS after crossing a permeabilized blood-brain barrier in the end stages of liver failure. Furthermore, the observation of low brain concentrations of quinolinic acid only in stage IV encephalopathy suggests that the contribution of quinolinic acid to the pathogenesis of hepatic encephalopathy in these animal models is minor.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Basile AS,Saito K,Li Y,Heyes MP

doi

10.1046/j.1471-4159.1995.64062607.x

subject

Has Abstract

pub_date

1995-06-01 00:00:00

pages

2607-14

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

64

pub_type

杂志文章

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