Inhibition of arginase activity ameliorates l-arginine-induced acute pancreatitis in rats

György Biczó, P. Hegyi, Sándor Berczi, Sándor Dósa, Zsuzsanna Hracskó, I. Varga, B. Iványi, V. Venglovecz, T. Wittmann, T. Takács, Z. Rakonczay

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)868-874
Number of pages7
JournalPancreas.
Volume39
Issue number6
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Arginase
Pancreatitis
Arginine
Acids
Citrulline
Injections
Ornithine
Glutathione Peroxidase
Heat-Shock Proteins
Intraperitoneal Injections
Peroxidase
Wistar Rats
Body Weight
Weights and Measures
Liver
Serum

Keywords

  • (+)-S-2-amino-6-iodoacetamidohexanoic acid
  • acute pancreatitis
  • arginase
  • L-arginine

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Inhibition of arginase activity ameliorates l-arginine-induced acute pancreatitis in rats. / Biczó, György; Hegyi, P.; Berczi, Sándor; Dósa, Sándor; Hracskó, Zsuzsanna; Varga, I.; Iványi, B.; Venglovecz, V.; Wittmann, T.; Takács, T.; Rakonczay, Z.

In: Pancreas., Vol. 39, No. 6, 08.2010, p. 868-874.

Research output: Contribution to journalArticle

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T1 - Inhibition of arginase activity ameliorates l-arginine-induced acute pancreatitis in rats

AU - Biczó, György

AU - Hegyi, P.

AU - Berczi, Sándor

AU - Dósa, Sándor

AU - Hracskó, Zsuzsanna

AU - Varga, I.

AU - Iványi, B.

AU - Venglovecz, V.

AU - Wittmann, T.

AU - Takács, T.

AU - Rakonczay, Z.

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N2 - 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.

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KW - L-arginine

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