Reference

L-Ornithine vs

L-Ornithine vs. L-ornithine-L-aspartate as a treatment for hyperammonemia-induced encephalopathy in rats. Vogels, B. A. P. M.; Karlsen, O. T.; Maas, M. A. W.; Bovee, W. M. M. J.; Chamuleau, R. A. F. M. (Academic Medical Center, Univ. Amsterdam, Amsterdam, Neth.). Journal of Hepatology, 26(1), 174-182 (English) 1997 Munksgaard. CODEN: JOHEEC. ISSN: 0168-8278. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effect of L-ornithine (ORN) and L-ornithine-L-aspartate (OA) therapy on "extracerebral" nitrogen metab., brain metab. and neurotransmission has been investigated in portacaval shunted rats with hyperammonemia-induced encephalopathy. One day before ammonium-acetate infusion, a portacaval shunt was performed in three exptl. groups: 1-control rats, 2-ORN-treated rats and 3 - OA-treated rats. Ammonium-acetate was given as an i.v. bolus injection (0.4 mmol×kg bw-1) followed by a const. infusion (1.9 mmol×kg bw-1×h-1) so that steady-state blood ammonia concns. (500-800 mM) were obtained in the course of 5 h. After 1 h, ammonium-acetate infusion, either L-ornithine or L-ornithine-L-aspartate, was infused for the next 4 h (3. 7664-41-7 and 3230-94-2 which are cas registry numbers of chemicals are mentioned.0 mmol×kg bw-1×h-1) in the treated groups. ORN and OA treatment resulted in significantly lower blood (34% and 39%) and brain (42% and 22%) ammonia concns., significantly higher urea prodn. (39% and 86%) and significantly smaller increases in brain glutamine and lactate concns. than in controls. These changes were assocd. with a significantly smaller increase in clin. grade of encephalopathy in ORN- and OA-treated rats, and a significant improvement in EEG activity in ORN-treated rats. OA-treated rats showed a significant increase in aspartate and glutamate concns. in brain dialyzate. The beneficial effects of both treatments on the manifestations of hyperammonemia-induced encephalopathy can be explained by a redn. in blood and brain ammonia concns. It is suggested that when OA is administered, the effect of ornithine is partly counteracted by aspartate, inducing high brain extracellular concns. of the two excitatory amino acids glutamate and aspartate, and perhaps causing overstimulation of NMDA receptors. .