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Inhibition of Arginase Activity Ameliorates L-Arginine-Induced Acute Pancreatitis in Rats

2010; Lippincott Williams & Wilkins; Volume: 39; Issue: 6 Linguagem: Inglês

10.1097/mpa.0b013e3181d371f8

1536-4828

György Biczó, Péter Hegyi, Sándor Berczi, Sándor Dósa, Zsuzsanna Hracskó, I Varga, Béla Iványi, Viktória Venglovecz, Tibor Wittmann, Tamás Takács, Zoltán Rakonczay,

Renal function and acid-base balance

Objectives: 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.