Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys
Mitigation of radiation nephropathy after internal α-particle irradiation of kidneys
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DOI：
10.1016/j.ijrobp.2005.11.036
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发表时间：
2006-04-01
影响因子：
7
通讯作者：
Scheinberg, DA
中科院分区：
文献类型：
--
作者：
Jaggi, JS;Seshan, SV;Scheinberg, DA
目的：放射免疫治疗、放射事故或核恐怖主义导致的肾脏内照射可导致放射性肾病。我们试图从药理学上改变注射锕（Ac-225）纳米发生器后小鼠肾脏的功能和形态变化，锕（Ac-225）纳米发生器是α和β粒子发射元素的体内发生器。方法与材料：给小鼠注射0.35 μ Ci的225Ac纳米发电机，给肾输送27.6 Gy的剂量。然后，他们随机接受卡托普利（血管紧张素转换酶抑制剂）、L-158,809（血管紧张素II受体阻滞剂）、螺内酯（醛固酮受体拮抗剂）或安慰剂。结果：注射225 Ac后40周，安慰剂对照组小鼠血尿素氮（BUN）显著升高（87.6 +/- 6.9 mg/dL）， Bowman间隙扩张，小管溶解伴基底膜增厚。卡托普利治疗加重了功能性损伤（BUN 119.0 +/- 4.0 mg/dl，与安慰剂对照组相比p < 0.01）和组织病理学损伤。相比之下，L-158,809提供中等保护（BUN 66.6 +/- 3.9 mg/dl, p = 0.02）。然而，螺内酯治疗显著阻止了组织病理学和功能变化的发展（BUN 31.2 +/- 2.5 mg/dl，与安慰剂对照组相比p < 0.001）。结论：小剂量的螺内酯和较小程度的血管紧张素受体- 1阻断剂对小鼠内部α颗粒照射模型具有肾脏保护作用。(c) 2006爱思唯尔公司
Purpose: Internal irradiation of kidneys as a consequence of radioimmunotherapy, radiation accidents, or nuclear terrorism can result in radiation nephropathy. We attempted to modify pharmacologically, the functional and morphologic changes in mouse kidneys after injection with the actinium (Ac-225) nanogenerator, an in vivo generator of alpha- and beta-particle emitting elements.Methods and Materials: The animals were injected with 0.35 mu Ci of the 225Ac nanogenerator, which delivers a dose of 27.6 Gy to the kidneys. Then, they were randomized to receive captopril (angiotensin-converting enzyme inhibitor), L-158,809 (angiotensin II receptor-I blocker), spironolactone (aldosterone receptor antagonist), or a placebo.Results: Forty weeks after the 225 Ac injection, the placebo-control mice showed a significant increase in blood urea nitrogen (BUN) (87.6 +/- 6.9 mg/dL), dilated Bowman spaces, and tubulolysis with basement membrane thickening. Captopril treatment accentuated the functional (BUN 119.0 +/- 4.0 mg/dl,; p < 0.01 vs. placebo controls) and histopathologic damage. In contrast, L-158,809 offered moderate protection (BUN 66.6 +/- 3.9 mg/dl,; p = 0.02 vs. placebo controls). Spironolactone treatment, however, significantly prevented the development of histopathologic and functional changes (BUN 31.2 +/- 2.5 mg/dl,; p < 0.001 vs. placebo controls).Conclusions: Low-dose spironolactone and, to a lesser extent, angiotensin receptor-I blockade can offer renal protection in a mouse model of internal alpha-particle irradiation. (c) 2006 Elsevier Inc.