Beneficial effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure induced by zymosan in the rat
Beneficial effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure induced by zymosan in the rat
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DOI：
10.1097/00003246-200101000-00022
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发表时间：
2001-01-01
影响因子：
8.8
通讯作者：
Thiemermann, C
中科院分区：
文献类型：
--
作者：
Cuzzocrea, S;McDonald, MC;Thiemermann, C
背景和方法：我们研究了Tempol（一种膜渗透性自由基清除剂）对酵母多糖所致大鼠多器官功能衰竭（MOF）的影响。酵母多糖（500 mg/kg，悬浮在盐水溶液中，ip）促进活性氧的形成，这有助于MOF的病理生理学。酵母多糖或生理盐水给药后，动物进行了监测12 day.Results：tempol（10，30，或100 mg/kg ip，酵母多糖后1和6小时）的大鼠治疗减弱了酵母多糖引起的腹膜渗出和多形核细胞的迁移，呈剂量依赖性。Tempol还减弱了肺、肝和肠损伤（组织学）以及酵母多糖引起的肺、肝和肠中髓过氧化物酶和丙二醛浓度的增加。硝基酪氨酸和聚（腺苷5 '-二磷酸核糖）合成酶的免疫组织化学分析表明，酵母多糖处理的大鼠的肺，肝和肠中的阳性染色。从接受tempol（100 mg/kg ip）的酵母多糖处理大鼠获得的组织切片中，硝基酪氨酸和聚（腺苷5 '-二磷酸核糖）合成酶的染色程度显著降低。此外，用tempol处理大鼠显著减少了以下各项：a）过氧亚硝酸盐的形成，B）DNA损伤，c）线粒体呼吸的损伤，以及d）在从用酵母聚糖处理的大鼠的腹腔收集的巨噬细胞中观察到的氧化型烟酰胺腺嘌呤二核苷酸的细胞浓度的降低。这项研究提供了第一个证据表明，tempol，一个小分子，渗透生物膜和清除活性氧，减弱程度的多器官功能衰竭与酵母多糖诱导的腹膜炎大鼠。
Background and Methods: We investigated the effects of tempol, a membrane-permeable radical scavenger, on the multiple organ failure (MOF) caused by zymosan in the rat. Zymosan (500 mg/kg, suspended in saline solution, ip) enhances formation of reactive oxygen species, which contribute to the pathophysiology of MOF. After zymosan or saline administration, animals were monitored for 12 days.Results: Treatment of rats with tempol (10, 30, or 100 mg/kg ip, 1 and 6 hrs after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan in a dose-dependent fashion. Tempol also attenuated the lung, liver, and intestinal injury (histology) as well as the increase in the concentrations of myeloperoxidase and malondialdehyde caused by zymosan in the lung, liver, and intestine. Immunohistochemical analysis for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose)synthetase demonstrated a positive staining in lung, liver, and intestine from zymosan-treated rats. The degree of staining for nitrotyrosine and for poly(adenosine 5'-diphosphate-ribose) synthetase was markedly reduced in tissue sections obtained from zymosan-treated rats that had received tempol (100 mg/kg ip). Furthermore, treatment of rats with tempol significantly reduced the following: a) the formation of peroxynitrite, b) the DNA damage, c) the impairment in mitochondrial respiration, and d) the decrease in the cellular concentration of oxidized nicotinamide adenine dinucleotide observed in macrophages harvested from the peritoneal cavity of rats treated with zymosan.Conclusion: This study provides the first evidence that tempol, a small molecule that permeates biological membranes and scavenges reactive oxygen species, attenuates the degree of MOF associated with zymosan-induced peritonitis in the rat.