Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis
Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis
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DOI：
10.1124/jpet.108.144451
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发表时间：
2009-01-01
影响因子：
3.5
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
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作者：
Ishihara, Tomoaki;Tanaka, Ken-Ichiro;Mizushima, Tohru
溃疡性结肠炎（UC）是由活性氧（ROS），特别是超氧阴离子（O2-）引起的肠粘膜损伤。超氧化物歧化酶（SOD）催化超氧阴离子歧化为过氧化氢，过氧化氢随后被过氧化氢酶解毒。卵磷脂化超氧化物歧化酶（PC-SOD）是一种新的SOD修饰形式，克服了以往SOD的临床局限性。在这项研究中，我们研究了PC-超氧化物歧化酶的行动使用UC的动物模型，葡聚糖硫酸钠（DSS）诱导的结肠炎。每日静脉注射PC-SOD可改善DSS诱导的结肠炎。未修饰的SOD产生类似的效果，但只有在超过30倍的浓度的PC-SOD。在体内电子自旋共振分析证实，增加与结肠炎的发展相关的ROS结肠水平被抑制PC-SOD管理。PCSOD的剂量-反应曲线呈钟形，但同时给予过氧化氢酶恢复了高剂量PC-SOD的改善效果。过氧化氢的积累与高剂量的PC-SOD，抑制过氧化氢酶的同时管理的效果的管理观察。我们还发现，无论是每周静脉注射或每天口服给药的PC-SOD提供保护。这些结果表明，PC-SOD通过降低结肠ROS水平来实现其对结肠炎的改善作用，并且其在较高剂量下的无效性是由于过氧化氢的积累。此外，我们认为间歇或口服PC-SOD可以应用于临床，以改善UC患者的生活质量。
Ulcerative colitis (UC) involves intestinal mucosal damage induced by reactive oxygen species (ROS), in particular, superoxide anion. Superoxide dismutase (SOD) catalyzes dismutation of superoxide anion to hydrogen peroxide, which is subsequently detoxified by catalase. Lecithinized SOD (PC-SOD) is a new modified form of SOD that has overcome previous clinical limitations of SOD. In this study, we examined the action of PC-SOD using an animal model of UC, dextran sulfate sodium (DSS)-induced colitis. DSS-induced colitis was ameliorated by daily intravenous administration of PC-SOD. Unmodified SOD produced a similar effect but only at more than 30 times the concentration of PC-SOD. In vivo electron spin resonance analysis confirmed that the increase in the colonic level of ROS associated with development of colitis was suppressed by PC-SOD administration. The dose-response profile of PCSOD was bell-shaped, but simultaneous administration of catalase restored the ameliorative effect at high doses of PC-SOD. Accumulation of hydrogen peroxide was observed with the administration of high doses of PC-SOD, an effect that was suppressed by the simultaneous administration of catalase. We also found that either a weekly intravenous administration or daily oral administration of PC-SOD conferred protection. These results suggest that PC-SOD achieves its ameliorative effect against colitis through decreasing the colonic level of ROS and that its ineffectiveness at higher doses is because of the accumulation of hydrogen peroxide. Furthermore, we consider that intermittent or oral administration of PC-SOD can be applied clinically to improve the quality of life of UC patients.