title: Inhibition of arginase activity ameliorates L-arginine-induced acute pancreatitis in rats.
abstract: OBJECTIVE
  Intraperitoneal (IP) injection of 3.5 g/kg L-arginine (known to induce acute pancreatitis) in rats will result in much greater increases in serum ornithine versus citrulline concentration (Crit Care Med. 2008;36:2117-2127). These data indicate a major role of arginase in the catabolism of L-arginine. Therefore, we tested the effects of the irreversible arginase inhibitor (+)-S-2-amino-6-iodoacetamidohexanoic acid (AIHA) on L-arginine-induced acute pancreatitis.
  
  
  METHODS
  The inhibitory effect of AIHA on arginase activity was tested on rat liver homogenate and purified bovine arginase. Male Wistar rats were administered 15 mg/kg AIHA or its vehicle IP 1 hour before the injection of physiological saline or 3.5 g/kg L-arginine IP. Laboratory and histological parameters of pancreatitis were determined 24 hours after the last injection.
  
  
  RESULTS
  Sixty micromolars of AIHA (equimolar to an in vivo dose of 15 mg/kg) significantly inhibited arginase activity by about 25%. Pretreatment with AIHA significantly ameliorated pancreatic damage caused by L-arginine administration. It decreased pancreatic weight/body weight ratio, pancreatic glutathione peroxidase and myeloperoxidase activities, and histological damage. Administration of AIHA in itself significantly increased levels of pancreatic heat shock proteins.
  
  
  CONCLUSIONS
  Pretreatment with AIHA reduces the severity of L-arginine-induced pancreatitis most likely by inhibiting arginase activity.
authors.affiliation: First Department of Medicine, University of Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Biczó
authors.forename: Péter
authors.initials: P
authors.lastname: Hegyi
authors.forename: Sándor
authors.initials: S
authors.lastname: Berczi
authors.forename: Sándor
authors.initials: S
authors.lastname: Dósa
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hracskó
authors.forename: Ilona S
authors.initials: IS
authors.lastname: Varga
authors.forename: Béla
authors.initials: B
authors.lastname: Iványi
authors.forename: Viktória
authors.initials: V
authors.lastname: Venglovecz
authors.forename: Tibor
authors.initials: T
authors.lastname: Wittmann
authors.forename: Tamás
authors.initials: T
authors.lastname: Takács
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Rakonczay
mesh_terms: D000208:Acute Disease; D000614:Aminocaproates; D015119:Aminocaproic Acid / Q000627:therapeutic use; D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors*; D001120:Arginine / Q000633:toxicity; D002417:Cattle; D002956:Citrulline / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis; D006360:Heat-Shock Proteins / Q000032:analysis; D008297:Male; D009952:Ornithine / Q000378:metabolism; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D000614:Aminocaproates; D006360:Heat-Shock Proteins; D002956:Citrulline; C079268:2-amino-6-iodoacetamidohexanoic acid; D001120:Arginine; D009952:Ornithine; D009195:Peroxidase; D005979:Glutathione Peroxidase; D001119:Arginase; D015119:Aminocaproic Acid