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Permalink: http://hdl.handle.net/1866/9581

L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action.

Article [Accepted Manuscript]
Thumbnail
Rose et al, 1998_MBD_OA PCA.pdf (472.9Kb)
Is part of
Metabolic Brain Disease ; 13(2)
1998-06
Author(s)
Rose, Christopher F.
Michalak, Adrianna
Pannunzio, Pierre
Therrien, Guy
Quack, Guenter
Kircheis, Gerald
Butterworth, Roger F.
Affiliation
  • Faculté de médecine
  • Centre de recherche du CHUM
Keywords
  • Ammonia
  • Ammoniac
  • Encéphalopathie hépatique
  • Glutamine synthesis
  • Hepatic Encephalopathy
  • L-Aspartate de L-ornithine
  • L-ornithine-L-aspartate
  • Portal-systemic Encephalopathy
Abstract(s)
Strategies aimed at the lowering of blood ammonia remain the treatment of choice in portal-systemic encephalopathy (PSE). L-ornithine-L-aspartate (OA) has recently been shown to be effective in the prevention of ammonia-precipitated coma in humans with PSE. These findings prompted the study of mechanisms of the protective effect of OA in portacaval-shunted rats in which reversible coma was precipitated by ammonium acetate administration (3.85 mmol/kg i.p.). OA infusions (300 mg/kg/h, i.v) offered complete protection in 12/12 animals compared to 0/12 saline-infused controls. This protective effect was accompanied by significant reductions of blood ammonia, concomitant increases of urea production and significant increases in blood and cerebrospinal fluid (CSF) glutamate and glutamine. Increased CSF concentrations of leucine and alanine also accompanied the protective effect of OA. These findings demonstrate the therapeutic efficacy of OA in the prevention of ammonia-precipitated coma in portacaval-shunted rats and suggest that this protective effect is both peripherally-mediated (increased urea and glutamine synthesis) and centrally-mediated (increased glutamine synthesis).
Rose, C., Michalak, A., Pannunzio, P., Therrien, G., Quack, G., Kircheis, G. and Butterworth, R. F. (1998) L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action. Metab Brain Dis 13(2):147-157
Other location(s)
http://dx.doi.org/10.1023/A:1020613314572
Collections
  • Faculté de médecine - Travaux et publications [217]

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