First Department of Medicine, University of Szeged, Hungary.
Pancreas. 2010 Aug;39(6):868-74. doi: 10.1097/MPA.0b013e3181d371f8.
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.
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.
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.
Pretreatment with AIHA reduces the severity of L-arginine-induced pancreatitis most likely by inhibiting arginase activity.
在大鼠中腹腔内注射 3.5 g/kg L-精氨酸（已知会引发急性胰腺炎），将导致血清鸟氨酸对瓜氨酸浓度的增加幅度显著大于 L-精氨酸（危重病医学。2008；36:2117-2127）。这些数据表明精氨酸酶在 L-精氨酸的分解代谢中起主要作用。因此，我们测试了不可逆精氨酸酶抑制剂（+）-S-2-氨基-6-碘乙酰氨基己酸（AIHA）对 L-精氨酸诱导的急性胰腺炎的影响。
在大鼠肝匀浆和纯化的牛精氨酸酶上测试了 AIHA 对精氨酸酶活性的抑制作用。雄性 Wistar 大鼠在腹腔注射生理盐水或 3.5 g/kg L-精氨酸前 1 小时，给予 15 mg/kg AIHA 或其载体。在最后一次注射后 24 小时，测定胰腺炎的实验室和组织学参数。
60 μmol 的 AIHA（相当于体内剂量 15 mg/kg）显著抑制了约 25%的精氨酸酶活性。AIHA 的预处理显著改善了 L-精氨酸给药引起的胰腺损伤。它降低了胰腺重量/体重比、胰腺谷胱甘肽过氧化物酶和髓过氧化物酶活性以及组织学损伤。AIHA 的自身给药显著增加了胰腺热休克蛋白的水平。
AIHA 的预处理通过抑制精氨酸酶活性，最有可能减轻 L-精氨酸诱导的胰腺炎的严重程度。
