L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats

Hepatology

Volumn 50, Issue 1, 2009, Pages 155-164

  Davies, Nathan A ^a   Wright, Gavin ^a   Ytrebø, Lars M ^b   Stadlbauer, Vanessa ^a   Fuskevåg, Ole Martin ^b   Zwingmann, Claudia ^c   Davies, D Ceri ^d   Habtesion, Abeba ^a   Hodges, Stephen J ^a   Jalan, Rajiv ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY HOSPITAL OF NORTH NORWAY   (Norway)

^c UNIVERSITÉ DE MONTRÉAL   (Canada)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 PHENYLBUTYRIC ACID; AMMONIA; CARBOXYLIC ACID; GLUTAMINE; INOSITOL; ORNITHINE; PHENYLACETIC ACID; PHENYLBUTYRIC ACID; UNCLASSIFIED DRUG; ARYLBUTYRIC ACID DERIVATIVE; PHENYLACETIC ACID DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE DUCT LIGATION; BRAIN METABOLISM; BRAIN WATER; CONTROLLED STUDY; DRUG POTENTIATION; DRUG RESPONSE; HYPERAMMONEMIA; LIVER CIRRHOSIS; MALE; NONHUMAN; PRIORITY JOURNAL; RAT; ANIMAL; BODY WATER; BRAIN; DRUG EFFECT; METABOLISM; SPRAGUE DAWLEY RAT;

AMMONIA; ANIMALS; BODY WATER; BRAIN; DRUG SYNERGISM; LIVER CIRRHOSIS; MALE; ORNITHINE; PHENYLACETATES; PHENYLBUTYRATES; RATS; RATS, SPRAGUE-DAWLEY;

EID: 67651146951     PISSN: 02709139     EISSN: None     Source Type: Journal    
DOI: 10.1002/hep.22897     Document Type: Article

References (37)

1. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. HEPATOLOGY 2002;35:716-721. (Pubitemid 34183979)
2. Jalan R, Damink SW, Deutz NE, Lee A, Hayes PC. Moderate hypothermia for uncontrolled intracranial hypertension in acute liver failure. Lancet 1999;354:1164-1168. (Pubitemid 29460446)
3. Strauss GI, Knudsen GM, Kondrup J, Moller K, Larsen FS. Cerebral metabolism of ammonia and amino acids in patients with fulminant hepatic failure. Gastroenterology 2001;121:1109-1119. (Pubitemid 33022091)
4. Balata S, Damink SW, Ferguson K, Marshall I, Hayes PC, Deutz NE, et al. Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis. HEPATOLOGY 2003;37:931-939. (Pubitemid 36401563)
5. Als-Nielsen B, Gluud LL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomised trials. Br Med J 2004;328:1046. (Pubitemid 38580827)
6. Shawcross D, Jalan R. Dispelling myths in the treatment of hepatic encephalopathy. Lancet 2005;365:431-433. (Pubitemid 40179231)
7. Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF. L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. HEPATOLOGY 1999;30:636-640. (Pubitemid 29409406)
8. Olde Damink SW, Deutz NE, Dejong CH, Soeters PB, Jalan R. Interorgan ammonia metabolism in liver failure. Neurochem Int 2002;41:177-188. (Pubitemid 34521691)
9. Olde Damink SW, Jalan R, Deutz NE, Redhead DN, Dejong CH, Hynd P, et al. The kidney plays a major role in the hyperammonemia seen after simulated or actual GI bleeding in patients with cirrhosis. HEPATOLOGY 2003;37:1277-1285. (Pubitemid 36667306)
10. Ytrebo LM, Sen S, Rose C, Davies NA, Nedredal GI, Fuskevaag OM, et al. Systemic and regional haemodynamics in pigs with acute liver failure and the effect of albumin dialysis. Scand J Gastroenterol 2006;41:1350-1360. (Pubitemid 44639309)
11. McFarlane Anderson N, Bennett FI, Alleyne GA. Ammonia production by the small intestine of the rat. Biochim Biophys Acta 1976;437:238-243.
12. Desjardins P, Rao KV, Michalak A, Rose C, Butterworth RF. Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle. Metab Brain Dis 1999;14:273-280. (Pubitemid 30337701)
13. Staedt U, Leweling H, Gladisch R, Kortsik C, Hagmuller E, Holm E. Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis: a double-blind, randomized study using a fourfold crossover design. J Hepatol 1993;19:424-430. (Pubitemid 24029921)
14. Kircheis G, Nilius R, Held C, Berndt H, Buchner M, Gortelmeyer R, et al. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, double- blind study. HEPATOLOGY 1997;25:1351-1360. (Pubitemid 27250753)
15. Jalan R, Wright G, Davies NA, Hodges SJ. L-ornithine phenylacetate (OP): a novel treatment for hyperammonemia and hepatic encephalopathy. Med Hypotheses 2007;69:1064-1069. (Pubitemid 47430227)
16. Smith I. The treatment of inborn errors of the urea cycle. Nature 1981; 291:378-380.
17. Wright G, Shawcross DL, Hodges S, Zwingmann C, Brooks HF, Mani A, et al. Endotoxemia produces coma and brain swelling in bile duct ligated rats. HEPATOLOGY 2007;45:1517-1526. (Pubitemid 46918336)
18. Harry D, Anand R, Holt S, Davies S, Marley R, Fernando B, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic rat. HEPATOLOGY 1999;30:1198-1205. (Pubitemid 29510858)
19. Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, et al. Endotoxemia produces coma and brain swelling in bile duct ligated rats. HEPATOLOGY 2007;45:1517-1526. (Pubitemid 46918336)
20. Davies NA, Brealey DA, Stidwill R, Singer M, Svistunenko DA, Cooper CE. Nitrosyl heme production compared in endotoxemic and hemorrhagic shock. Free Radic Biol Med 2005;38:41-49. (Pubitemid 39626907)
21. van Eijk HM, Rooyakkers DR, Deutz NE. Rapid routine determination of amino acids in plasma by high-performance liquid chromatography with a 2-3 microns Spherisorb ODS II column. J Chromatogr 1993;620:143-148.
22. Neeley WE, Phillipson J. Automated enzymatic method for determining ammonia in plasma, with 14-day reagent stability. Clin Chem 1988;34: 1868-1869. (Pubitemid 18235423)
23. Stewart-Wallace AM. A biochemical study of cerbral tissue, and of changes in cerbral oedema. Brain 1939;62:426-438.
24. Traber PG, Ganger DR, Blei AT. Brain edema in rabbits with galactosamine- induced fulminant hepatitis: regional differences and effects on intracranial pressure. Gastroenterology 1986;91:1347-1356.
25. Zwingmann C, Chatauret N, Leibfritz D, Butterworth RF. Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H-C] nuclear magnetic resonance study. HEPATOLOGY 2003;37:420-428. (Pubitemid 36152542)
26. Kriat M, Confort-Gouny S, Vion-Dury J, Sciaky M, Viout P, Cozzone PJ. Quantitation of metabolites in human blood serum by proton magnetic resonance spectroscopy: a comparative study of the use of formate and TSP as concentration standards. NMR Biomed 1992;5:179-184.
27. Buckner JC, Malkin MG, Reed E, Cascino TL, Reid JM, Ames MM, et al. Phase II study of antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in patients with recurrent glioma. Mayo Clin Proc 1999;74:137-145. (Pubitemid 29085209)
28. Kasumov T, Brunengraber LL, Comte B, Puchowicz MA, Jobbins K, Thomas K, et al. New secondary metabolites of phenylbutyrate in humans and rats. Drug Metab Dispos 2004;32:10-19. (Pubitemid 38112530)
29. Ytrebø LMK, Gangsøy R, Mæhre H, Fuskevåg OM, Kalstad T, Revhaug A, et al. L-Ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure [Abstract]. HEPATOLOGY 2007;46:275A.
30. Haussinger D, Laubenberger J, vom Dahl S, Ernst T, Bayer S, Langer M, et al. Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy. Gastroenterology 1994;107:1475-1480.
31. Cordoba J, Gottstein J, Blei AT. Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: implications for ammonia-induced brain edema. HEPATOLOGY 1996;24:919-923. (Pubitemid 26334295)
32. Shawcross DL, Balata S, Olde Damink SW, Hayes PC, Wardlaw J, Marshall I, et al. Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia. Am J Physiol Gastrointest Liver Physiol 2004;287: G503-G509. (Pubitemid 39096614)
33. Zwingmann C, Leibfritz D. Ammonia toxicity under hyponatremic conditions in astrocytes: de novo synthesis of amino acids for the osmoregulatory response. Neurochem Int 2005;47:39-50. (Pubitemid 40848691)
34. Restuccia T, Gomez-Anson B, Guevara M, Alessandria C, Torre A, Alayrach ME, et al. Effects of dilutional hyponatremia on brain organic osmolytes and water content in patients with cirrhosis. HEPATOLOGY 2004; 39:1613-1622. (Pubitemid 38702662)
35. Haseler LJ, Sibbitt WL Jr, Mojtahedzadeh HN, Reddy S, Agarwal VP, McCarthy DM. Proton MR spectroscopic measurement of neurometabolites in hepatic encephalopathy during oral lactulose therapy. AJNR Am J Neuroradiol 1998 Oct;199):1681-1686. (Pubitemid 30413759)
36. Patishi Y, Lubrich B, Berger M, Kofman O, van Calker D, Belmaker RH. Differential uptake of myo-inositol in vivo into rat brain areas. Eur Neuropsychopharmacol 1996;6:73-75. (Pubitemid 26100035)
37. Yamashita T, Shimada S, Yamauchi A, Guo W, Kohmura E, Hayakawa T, et al. Induction of Na+/myo-inositol co-transporter mRNA after rat cryogenic injury. Brain Res Mol Brain Res 1997;46:236-242. (Pubitemid 27218306)