Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 302, Issue 1, 2012, Pages

  Balasubramaniyan, Vairappan ^a   Wright, Gavin ^a   Sharma, Vikram ^a   Davies, Nathan A ^a   Sharifi, Yalda ^a   Habtesion, Abeba ^a   Mookerjee, Rajeshwar P ^a   Jalan, Rajiv ^a  

^a ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Blood flow; Cirrhosis; Hepatic encephalopathy; Inflammation; Oxidant injury

Indexed keywords

AMMONIA; DIMETHYLARGININASE; ENDOTHELIAL NITRIC OXIDE SYNTHASE; N(G),N(G) DIMETHYLARGININE; ORNITHINE DERIVATIVE; ORNITHINE PHENYLACETATE; PHENYLACETIC ACID DERIVATIVE; PLACEBO; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SODIUM CHLORIDE; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

AMMONIA BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BILE DUCT LIGATION; BRAIN WATER; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME BLOOD LEVEL; HEPATIC ENCEPHALOPATHY; LIVER CIRRHOSIS; MALE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RADIOMETRY; RANDOMIZED CONTROLLED TRIAL; RAT; REDUCTION; SHAM PROCEDURE; SPRAGUE DAWLEY RAT; WESTERN BLOTTING;

AMIDOHYDROLASES; AMMONIA; ANIMALS; ARGININE; BILE DUCTS; BRAIN; LIGATION; LIVER CIRRHOSIS; MALE; NADPH OXIDASE; NITRIC OXIDE SYNTHASE TYPE III; ORNITHINE; PHENYLACETATES; RATS; RATS, SPRAGUE-DAWLEY; TUMOR NECROSIS FACTOR-ALPHA;

EID: 83755177664     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00097.2011     Document Type: Article

References (45)

1. Balasubramaniyan V, Sharma V, Davies NA, Jalan R, Mookerjee RP. Modulation of the DDAH-ADMA pathway with the Farnesoid receptor (FXR) agonist INT-747 restores hepatic eNOS activity and lowers portal pressure in cirrhotic rats (Abstract). Hepatology 50: 336A-337A, 2009.
2. Cauli O, Rodrigo R, Boix J, Piedrafita B, Agusti A, Felipo V. Acute liver failure-induced death of rats is delayed or prevented by blocking NMDA receptors in brain. Am J Physiol Gastrointest Liver Physiol 295: G503-G511, 2008.
3. Cauli OR, Rodrigo R, Piedrafita B, Boix JB, Felipo V. Inflammation and hepatic encephalopathy: ibuprofen restores learning ability in rats with portacaval shunts. Hepatology 46: 514-509, 2007.
4. Corbalan R, Montoliu C, Minana MD, Del Olmo JA, Serra MA, Aparisi L, Rodrigo JM, Felipo V. Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease. Metab Brain Dis 17: 295-301, 2002.
5. Davies NA, Wright G, Ytrebo LM, Stadlbauer V, Fuskevag OM, Zwingmann C, Davies DC, Habtesion A, Hodges SJ, Jalan R. L-ornithine and phenylacetate synergistically produce sustained reduction in ammonia and brain water in cirrhotic rats. Hepatology 50: 155-164, 2009.
6. Dillon JF, Plevris JN, Wong FC, Chan KH, Lo NT, Miller JD, Bouchier IA, Hayes PC. Middle cerebral artery blood flow velocity in patients with cirrhosis. Eur J Gastroenterol Hepatol 7: 1087-1091, 1995.
7. Elmlili N, Boix J, Ahabrach H, Rodrigo R, Errami M, Felipo V. Chronic hyperammonemia induces tonic activation of NMDA receptors in cerebellum. J Neurochem 112: 1005-1014, 2010.
8. Erceg S, Monfort P, Hernandez-Viadel M, Rodrigo R, Montoliu C, Felipo V. Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology 41: 299-306, 2005.
9. Faraci FM, Brian JE Jr, Heistad DD. Response of cerebral blood vessels to an endogenous inhibitor of nitric oxide synthase. Am J Physiol Heart Circ Physiol 269: H1522-H1527, 1995.
10. Giovannoni G, Land JM, Keir G, Thompson EJ, Heales SJ. Adaptation of the nitrate reductase and Griess reaction methods for the measurement of serum nitrate plus nitrite levels. Ann Clin Biochem 34: 193-198, 1997.
11. Guevara M, Bru C, Gines P, Fernandez-Esparrach G, Sort P, Bataller R, Jimenez W, Arroyo V, Rodes. Increased cerebrovascular resistance in cirrhotic patients with ascites. Hepatology 28: 39-44, 1998.
12. Harry D, Anand R, Holt S, Davies S, Marley R, Fernando B, Goodier D, Moore K. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic rat. Hepatology 30: 1198-1205, 1999.
13. Haussinger D, Schliess F. Astrocyte swelling and protein tyrosine nitration in hepatic encephalopathy. Neurochem Int 47: 64-70, 2005.
14. Hermenegildo C, Montoliu C, Llansola M, Munoz MD, Gaztelu JM, Minana MD, Felipo V. Chronic hyperammonemia impairs the glutamatenitric oxide-cyclic GMP pathway in cerebellar neurons in culture and in the rat in vivo. Eur J Neurosci 10: 3201-3209, 1998.
15. Jalan R, Olde Damink SW, Hayes PC, Deutz NE, Lee A. Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow. J Hepatol 41: 613-620, 2004.
16. Jalan R, Olde Damink SW, Lui HF, Glabus M, Deutz NE, Hayes PC, Ebmeier K. Oral amino acid load mimicking hemoglobin results in reduced regional cerebral perfusion and deterioration in memory tests in patients with cirrhosis of the liver. Metab Brain Dis 18: 37-49, 2003.
17. Jiang W, Desjardins P, Butterworth RF. Cerebral inflammation contributes to encephalopathy and brain edema in acute liver failure: protective effect of minocycline. J Neurochem 109: 485-493, 2009.
18. Jiang W, Desjardins P, Butterworth RF. Direct evidence for central proinflammatory mechanisms in rats with experimental acute liver failure: protective effect of hypothermia. J Cereb Blood Flow Metab 29: 944-952, 2009.
19. Kielstein JT, Donnerstag F, Gasper S, Menne J, Kielstein A, Martens- Lobenhoffer J, Scalera F, Cooke JP, Fliser D, Bode-Boger SM. ADMA increases arterial stiffness and decreases cerebral blood flow in humans. Stroke 37: 2024-2029, 2006.
20. Lagi A, La Villa G, Barletta G, Cencetti S, Bacalli S, Cipriani M, Foschi M, Lazzeri C, Del Bene R, Gentilini P, Laffi G. Cerebral autoregulation in patients with cirrhosis and ascites. A transcranial Doppler study. J Hepatol 27: 114-120, 1997.
21. Larsen FS, Adel Hansen B, Pott F, Ejlersen E, Secher NH, Paulson OB, Knudsen GM. Dissociated cerebral vasoparalysis in acute liver failure. A hypothesis of gradual cerebral hyperaemia. J Hepatol 25: 145-151, 1996.
22. Leiper J, Nandi M, Torondel B, Murray-Rust J, Malaki M, O'Hara B, Rossiter S, Anthony S, Madhani M, Selwood D, Smith C, Wojciak- Stothard B, Rudiger A, Stidwill R, McDonald NQ, Vallance P. Disruption of methylarginine metabolism impairs vascular homeostasis. Nat Med 13: 198-203, 2007.
23. Leiper J, Vallance P. Biological significance of endogenous methylarginines that inhibit nitric oxide synthases. Cardiovasc Res 43: 542-548, 1999.
24. Leiper JM, Santa Maria J, Chubb A, MacAllister RJ, Charles IG, Whitley GS, Vallance P. Identification of two human dimethylarginine dimethylaminohydrolases with distinct tissue distributions and homology with microbial arginine deiminases. Biochem J 343: 209-214, 1999.
25. Marmarou A, Tanaka K, Shulman K. An improved gravimetric measure of cerebral edema. J Neurosurg 56: 246-253, 1982.
26. Matkowskyj KA, Marrero JA, Carroll RE, Danilkovich AV, Green RM, Benya RV. Azoxymethane-induced fulminant hepatic failure in C57BL/6J mice: characterization of a new animal model. Am J Physiol Gastrointest Liver Physiol 277: G455-G462, 1999.
27. Monfort P, Munoz MD, ElAyadi A, Kosenko E, Felipo V. Effects of hyperammonemia and liver failure on glutamatergic neurotransmission. Metab Brain Dis 17: 237-250, 2002.
28. Montoliu C, Rodrigo R, Monfort P, Llansola M, Cauli O, Boix J, Elmlili N, Agusti A, Felipo V. Cyclic GMP pathways in hepatic encephalopathy. Neurological and therapeutic implications. Metab Brain Dis 25: 39-48, 2010.
29. Mookerjee RP, Dalton RN, Davies NA, Hodges SJ, Turner C, Williams R, Jalan R. Inflammation is an important determinant of levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in acute liver failure. Liver Transpl 13: 400-405, 2007.
30. Mookerjee RP, Malaki M, Davies NA, Hodges SJ, Dalton RN, Turner C, Sen S, Williams R, Leiper J, Vallance P, Jalan R. Increasing dimethylarginine levels are associated with adverse clinical outcome in severe alcoholic hepatitis. Hepatology 45: 62-71, 2007.
31. Mookerjee RP, Wiesenthal A, Icking A, Hodges SJ, Davies NA, Schilling K, Sen S, Williams R, Novelli M, Muller-Esterl W, Jalan R. Increased gene and protein expression of the novel eNOS regulatory protein NOSTRIN and a variant in alcoholic hepatitis. Gastroenterology 132: 2533-2541, 2007.
32. Norenberg MD. Oxidative and nitrosative stress in ammonia neurotoxicity. Hepatology 37: 245-248, 2003.
33. Norenberg MD, Rao KV, Jayakumar AR. Mechanisms of ammoniainduced astrocyte swelling. Metab Brain Dis 20: 303-318, 2005.
34. Pope AJ, Druhan L, Guzman JE, Forbes SP, Murugesan V, Lu D, Xia Y, Chicoine LG, Parinandi NL, Cardounel AJ. Role of DDAH-1 in lipid peroxidation product-mediated inhibition of endothelial NO generation. Am J Physiol Cell Physiol 293: C1679-C1686, 2007.
35. Reinehr R, Gorg B, Becker S, Qvartskhava N, Bidmon HJ, Selbach O, Haas HL, Schliess F, Haussinger D. Hypoosmotic swelling and ammonia increase oxidative stress by NADPH oxidase in cultured astrocytes and vital brain slices. Glia 55: 758-771, 2007.
36. Rodrigo R, Cauli O, Gomez-Pinedo U, Agusti A, Hernandez-Rabaza V, Garcia-Verdugo JM, Felipo V. Hyperammonemia induces neuroinflammation that contributes to cognitive impairment in rats with hepatic encephalopathy. Gastroenterology 139: 675-684, 2010.
37. Sen S, Rose C, Ytrebo LM, Davies NA, Nedredal GI, Drevland SS, Kjonno M, Prinzen FW, Hodges SJ, Deutz NE, Williams R, Butterworth RF, Revhaug A, Jalan R. Effect of albumin dialysis on intracranial pressure increase in pigs with acute liver failure: a randomized study. Crit Care Med 34: 158-164, 2006.
38. Shawcross D, Jalan R. The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cell Mol Life Sci 62: 2295-2304, 2005.
39. Sinke AP, Jayakumar AR, Panickar KS, Moriyama M, Reddy PV, Norenberg MD. NFkappaB in the mechanism of ammonia-induced astrocyte swelling in culture. J Neurochem 106: 2302-2311, 2008.
40. Stewart-Wallace AM. A biochemical study of cerebral tissue, and of changes in cerbral oedema. Brain 62: 426-438, 1939.
41. Ueno S, Sano A, Kotani K, Kondoh K, Kakimoto Y. Distribution of free methylarginines in rat tissues and in the bovine brain. J Neurochem 59: 2012-2016, 1992.
42. Vallance P, Leone A, Calver A, Collier J, Moncada S. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339: 572-575, 1992.
43. Vaquero JC, Chung ME, Blei C. Nitrotyrosine and nitric oxide synthase in the brain of rats with ammonia-induced brain edema. Semin Liv Dis 23: 259-269, 2003.
44. Wright G, Davies NA, Shawcross DL, Hodges SJ, Zwingmann C, Brooks HF, Mani AR, Harry D, Stadlbauer V, Zou Z, Williams R, Davies C, Moore KP, Jalan R. Endotoxemia produces coma and brain swelling in bile duct ligated rats. Hepatology 45: 1517-1526, 2007.
45. Ytrebø LM, Kristiansen RG, Maehre H, Fuskevag OM, Kalstad T, Revhaug A, Cobos MJ, Jalan R, Rose CF. L-ornithine phenylacetate attenuates increased arterial and extracellular brain ammonia and prevents intracranial hypertension in pigs with acute liver failure. Hepatology 50: 165-174, 2009.