Maksimenko A V, Petrov A D, Caliceti P, Konovalova G G, Schiavon O, Grigor'eva E L, Lankin V Z, Veronese F M
Institute of Experimental Cardiology, Cardiology Research Center, Russian Academy of Medical Sciences, Moscow.
Eksp Klin Farmakol. 1993 Sep-Oct;56(5):14-8.
Mice were used to make a comparative study of the biological distribution of intravenous preparations of native and monomethoxypolyethylene glycol-modified superoxide dismutase isolated from bovine liver, as well as native and aldehyde dextran. The study demonstrated that the biodistribution of the native enzymes from various sources was, however, equal, but in the mouse liver there was a higher accumulation of SOD isolated from the rat liver. AD-SOD was found to have a longer half-life in the blood and in the liver of mice, in particular, while MPEG-SOD showed 10, 15, and 16 times longer in the lungs, blood and heart of the animals examined, respectively. The elevated accumulation of MPEG-SOD in some organs was used for their treatment, particularly for experimental therapy of rat myocardial ischemia. A rat model of ischemia demonstrated that the intravenous bolus administration of MPEG-SOD reduced the size of a myocardial necrotic area by 40% as compared to a 13% decrease when the other compounds were assayed. The findings suggest that the MPEG-SOD preparation is promising for decreasing reperfusion injuries of the cardiovascular system and the lungs.
利用小鼠对从牛肝中分离出的天然超氧化物歧化酶和单甲氧基聚乙二醇修饰的超氧化物歧化酶静脉制剂以及天然醛葡聚糖和醛修饰葡聚糖的生物分布进行了比较研究。然而,研究表明,不同来源的天然酶的生物分布是相同的,但在小鼠肝脏中,从大鼠肝脏分离出的超氧化物歧化酶积累量更高。发现醛修饰超氧化物歧化酶在小鼠血液和肝脏中的半衰期更长,特别是在动物的肺、血液和心脏中,单甲氧基聚乙二醇修饰的超氧化物歧化酶的半衰期分别长10倍、15倍和16倍。单甲氧基聚乙二醇修饰的超氧化物歧化酶在某些器官中的积累增加被用于这些器官的治疗,特别是用于大鼠心肌缺血的实验治疗。缺血大鼠模型表明,与测定其他化合物时心肌坏死面积减少13%相比,静脉推注单甲氧基聚乙二醇修饰的超氧化物歧化酶可使心肌坏死面积减少40%。这些发现表明,单甲氧基聚乙二醇修饰的超氧化物歧化酶制剂在减少心血管系统和肺部的再灌注损伤方面具有前景。