title: Presence of methylated arginine derivatives in orthotopic human liver transplantation: relevance for liver function.
abstract: Orthotopic liver transplantation (OLT) is a frequent option in the treatment of liver diseases. During the cold ischemia period of the donor liver, there is an accumulation of metabolites that are potent inhibitors of the cytokine-inducible and endothelial nitric oxide synthase isoenzymes. We identified the presence of L-N-monomethylarginine and asymmetric dimethylarginine (ADMA) as the main inhibitors by means of analytic high-pressure liquid chromatography and mass spectrometry techniques. An average ADMA concentration of 450 micromol/L was measured in the preservation medium of donor livers with poor outcomes after OLT. A statistically significant relationship was observed between the concentration of methylated arginine derivatives in the graft and liver function after OLT. These data suggest that measurement of methylated arginine, released after liver protein catabolism, might provide an indication of functional status of the liver that can help the development of strategies intended to improve graft viability.
authors.affiliation: Instituto de Bioquímica, Centro Mixto Cousejo Superior de Investigacious Científicas-Universidad Compluteuse de Madrid (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Martín-Sanz
authors.forename: Luis
authors.initials: L
authors.lastname: Olmedilla
authors.forename: Elena
authors.initials: E
authors.lastname: Dulin
authors.forename: Marta
authors.initials: M
authors.lastname: Casado
authors.forename: Nuria A
authors.initials: NA
authors.lastname: Callejas
authors.forename: José
authors.initials: J
authors.lastname: Pérez-Peña
authors.forename: Ignacio
authors.initials: I
authors.lastname: Garutti
authors.forename: Javier
authors.initials: J
authors.lastname: Sanz
authors.forename: Javier
authors.initials: J
authors.lastname: Calleja
authors.forename: Santos
authors.initials: S
authors.lastname: Barrigón
authors.forename: Lisardo
authors.initials: L
authors.lastname: Boscá
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000302:isolation & purification*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005260:Female; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D016031:Liver Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011184:Postoperative Period; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase