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Abstract

Strategies aimed at the lowering of blood ammonia remain the treament 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-shuntedrats and suggest that this protective effect is both peripherally-mediated (increased urea and glutamine synthesis) and centrally-mediated (increased glutamine synthesis).

The Pharmabiotic Approach to Treat Hyperammonemia

“…l -Ornithine is transformed to glutamate semialdehyde by ornithine aminotransferase, which is subsequently converted to glutamate. Finally, glutamate converts to glutamine, which detoxifies one ammonia molecule by glutamine synthetase [ 85 , 44 ]. The intravenous and oral administration of l -ornithine- l -aspartate successfully improved venous ammonia levels and cognitive abilities in HE patients [ 45 , 46 ].…”

l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease

“…However, there are a few preclinical studies which could indicate a possible effect of LOLA on NAFLD. Two studies in experimental cirrhosis and HE described that ammonia lowering improved sarcopenia in cirrhotic Sprague–Dawley rats by stabilizing amino acid metabolism [22], and that LOLA treatment resulted in a significant increase of plasma glutamine, which probably derived from l -ornithine via GS [23]. Glutamine has been shown to be protective in preclinical models of NAFLD and NASH, possibly by reducing oxidative stress [24, 25].…”

Effect of l-ornithine l-aspartate against thioacetamide-induced hepatic damage in rats

“…It has been studied extensively and proven to be effective in both experimental as well as clinical set up of hepatic encephalopathy (HE). [12] HE is caused by hyperammonemia[34] that may be caused by insufficient removal of ammonia from blood by liver due to its compromised functional status[5] or portacaval shunting. [6] Hyperammonemia leads to increased levels of ammonia in brain, which is responsible for the development of HE.…”