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.
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.
Authors: Balázs Kui; Zsolt Balla; Eszter T Végh; Petra Pallagi; Viktória Venglovecz; Béla Iványi; Tamás Takács; Péter Hegyi; Zoltán Rakonczay Journal: Lab Invest Date: 2013-12-23 Impact factor: 5.662
Authors: Luiza A Rabelo; Fernanda O Ferreira; Valéria Nunes-Souza; Lucas José Sá da Fonseca; Marília O F Goulart Journal: Oxid Med Cell Longev Date: 2015-05-04 Impact factor: 6.543
Authors: Gabriele Netzel; Eddie T T Tan; Mukan Yin; Cindy Giles; Ken W L Yong; Rafat Al Jassim; Mary T Fletcher Journal: Toxins (Basel) Date: 2019-03-19 Impact factor: 4.546
Authors: Xiaoying Zhang; Tao Jin; Na Shi; Linbo Yao; Xinmin Yang; Chenxia Han; Li Wen; Dan Du; Peter Szatmary; Rajarshi Mukherjee; Tingting Liu; Qing Xia; David N Criddle; Wei Huang; Michael Chvanov; Robert Sutton Journal: Front Physiol Date: 2019-01-15 Impact factor: 4.566