L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action
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23 avril 2013
- handle: 10670/1.72j06i
- doi: 10.1023/A:1020613314572
Mots-clés
Ammonia Ammoniac Encéphalopathie hépatique Glutamine synthesis Hepatic Encephalopathy L-Aspartate de L-ornithine L-ornithine-L-aspartate Portal-systemic EncephalopathySujets proches
Portal-systemic encephalopathy Encephalopathy, Hepatic Portosystemic encephalopathy Porto-hepatic encephalopathyCiter ce document
Christopher Rose et al., « L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action », Papyrus : le dépôt institutionnel de l'Université de Montréal, ID : 10.1023/A:1020613314572
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Résumé
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).