title: Changes in Biliary Levels of Arginine and its Methylated Derivatives after Hepatic Ischaemia/Reperfusion.
abstract: Arginine (Arg) can be methylated to form symmetrical dimethylarginine (SDMA) and asymmetrical dimethylarginine (ADMA), the latter an endogenous inhibitor of nitric oxide synthase (NOS). SDMA is excreted in the urine, while ADMA is mainly subjected to degradation in the liver. Arg competes with ADMA and SDMA for cellular transport across cationic amino-acid transporters (CATs). We evaluated the changes in serum, tissue and biliary levels of Arg, citrulline (Cit), ADMA and SDMA and the modifications in CATs after ischaemia-reperfusion (I/R). Male Wistar rats were subjected to 30-min. partial-hepatic ischaemia or sham-operated. After 60-min. reperfusion, the concentrations of ADMA, SDMA, Arg and Cit in serum, tissue and bile were measured. Serum levels of AST, ALT and alkaline phosphatase (AP) levels were determined. mRNA of cationic transporter 2A (CAT-2A) and 2B (CAT-2B) were also quantified. An increase in ADMA and a decrease in SDMA were observed in bile at the end of reperfusion. On the contrary, lower tissue ADMA levels and higher SDMA levels were quantified. No serum changes in ADMA and SDMA were found. A decrease in Arg and an increase of Cit were detected in serum, bile and tissue after I/R. A marked increase in AST, ALT and AP levels in serum confirmed I/R injury. A decrease in mRNA transporter CAT-2A but not in CAT-2B was detected. This study supported a biliary CAT-2B-dependent transport of ADMA and demonstrated, for the first time, that the liver is also responsible for the biliary excretion of SDMA into the bile.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrigno
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Laura Giuseppina
authors.initials: LG
authors.lastname: Di Pasqua
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Berardo
authors.affiliation: Department of Molecular Medicine, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Rizzo
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Plinio
authors.initials: P
authors.lastname: Richelmi
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Mariapia
authors.initials: M
authors.lastname: Vairetti
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D026923:Amino Acid Transport Systems, Basic / Q000097:blood; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000737:chemistry*; D001219:Aspartate Aminotransferases / Q000097:blood; D001646:Bile / Q000737:chemistry*; D002956:Citrulline / Q000097:blood; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000097:blood* / Q000175:diagnosis; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood* / Q000473:pathology
chemical_list: D026923:Amino Acid Transport Systems, Basic; D012333:RNA, Messenger; C490274:Slc7a2 protein, rat; D002956:Citrulline; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D000581:Amidohydrolases; C059999:dimethylargininase