Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis
Oxidative stress in distant organs and the effects of allopurinol during experimental acute pancreatitis
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DOI：
10.1385/ijgc:27:3:209
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发表时间：
2000-06-01
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影响因子：
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通讯作者：
Lonovics, J
中科院分区：
文献类型：
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作者：
Czakó, L;Takács, T;Lonovics, J
背景本研究旨在评估氧自由基在L-精氨酸（Arg）诱导的急性胰腺炎局部和全身表现发展中的作用，并评估黄嘌呤氧化酶抑制剂别嘌呤醇的保护作用。在雄性Wistar大鼠中，通过以1小时的间隔腹膜内注射2 × 250 mg/100 g体重的精氨酸（20%的0.15 M NaCl溶液）诱导急性胰腺炎。对照组大鼠接受相同数量的甘氨酸。在第三组中，在第一次精氨酸注射前30分钟皮下给予200 mg/kg别嘌呤醇。分别在给药后6、12、24或48 h处死大鼠。急性胰腺炎通过血清淀粉酶水平升高和显微镜下观察到的典型炎症特征来证实。测定胰腺、肝脏和肾脏中丙二醛（MDA）、超氧化物歧化酶（Mn-和Cu，Zn-SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶的组织浓度。各器官组织MDA含量均显著升高。胰腺和肾脏中Mn-SOD、Cu，Zn-SOD、GPx和过氧化氢酶的活性迅速下降，而肝脏中只有Mn-SOD和GPx活性下降。组织学检查显示胰腺腺泡细胞坏死，但肝脏和肾脏仅轻度改变。别嘌呤醇预处理可阻止胰腺中活性氧代谢产物的产生，并减少其在肾脏中的形成。在Arg诱导的急性胰腺炎的早期阶段，氧源性自由基在胰腺、肝脏和肾脏中产生。肝脏和肾脏，但不是胰腺，能够抵御氧化应激。预防性应用别嘌呤醇可显著抑制胰腺和肾脏中自由基的产生。
Background. The present study was aimed at an assessment of the role of oxygen-derived free radicals in the development of local and systemic manifestations of L-arginine (Arg)-induced acute pancreatitis and at an evaluation of the protective effect of the xanthine oxidase inhibitor allopurinol.Methods. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally at an interval of 1 h, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. In a third group, 200 mg/kg of allopurinol was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, or 48 h following Arg administration. acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features were observed microscopically. Tissue concentrations of malonyl dialdehyde (MDA), superoxide dismutase (Mn- and Cu,Zn-SOD), glutathione peroxidase (GPx), and catalase were measured in the pancreas, liver, and kidney.Results. The tissue concentration of MDA was significantly elevated in each organ. The activities of Mn-SOD, Cu,Zn-SOD, GPx, and catalase were quickly depleted in the pancreas and kidney, whereas only the Mn-SOD and GPx activities were reduced in the liver after the onset of pancreatitis. Histologic examination revealed acinar cell necrosis in the pancreas, but only mild alterations in the liver and kidney. Allopurinol pretreatment prevented the generation of reactive oxygen metabolites in the pancreas and reduced their formation in the kidney.Conclusion. Oxygen-derived free radicals are generated in the pancreas, liver, and kidney at an early stage of Arg-induced acute pancreatitis. The liver and the kidney, but not the pancreas, are able to defend against oxidative stress. The prophylactic application of allopurinol significantly restrains the generation of free radicals in pancreas and kidney.