A Combination of Iohexol Treatment and Ionizing Radiation Exposure Enhances Kidney Injury in Contrast-Induced Nephropathy by Increasing DNA Damage
A Combination of Iohexol Treatment and Ionizing Radiation Exposure Enhances Kidney Injury in Contrast-Induced Nephropathy by Increasing DNA Damage
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DOI：
10.1667/rade-21-00178.1
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发表时间：
2022-04-01
影响因子：
3.4
通讯作者：
Tashiro, Satoshi
中科院分区：
文献类型：
--
作者：
Fujino, Shu;Sun, Jying;Tashiro, Satoshi
造影剂已经显示出诱发肾病（即，造影剂诱发的肾病）。造影剂肾病的分子机制尚不清楚。在这项研究中，我们研究了造影剂和电离辐射联合治疗对体外肾细胞和体内肾组织的影响，从而探讨了造影剂肾病的机制。在人肾小管上皮细胞中，免疫荧光分析显示碘海醇增加了辐射诱导的γ H2 AX核灶的数量。γ H2 AX核灶的数量在24 h时仍然很高，表明在碘海醇存在下，一些辐射诱导的双链断裂仍然未修复。我们建立了一个对比剂诱导的肾病小鼠模型，然后显示碘海醇和电离辐射协同降低肾功能并诱导双链断裂。重要的是，在不存在电离辐射的情况下，碘海醇在造影剂诱导的肾病模型小鼠的肾脏中诱导显著的巨噬细胞蓄积和氧化DNA损伤;这些效应被电离辐射放大。结果表明，碘海醇引起的潜在炎症和氧化DNA损伤有助于增强辐射诱导的双链断裂，导致造影剂诱导的肾病。(C)2022辐射研究学会
Contrast media has been shown to induce nephropathy (i.e., contrast-induced nephropathy) after various types of radiological examinations. The molecular mechanism of contrast-induced nephropathy has been unclear. In this study, we investigated the mechanism of contrast-induced nephropathy by examining the effects of combined treatment of contrast medium and ionizing radiation on kidney cells in vitro and kidney tissue in vivo. In human renal tubular epithelium cells, immunofluorescence analysis revealed that iohexol increased the numbers of radiation-induced gamma H2AX nuclear foci. The numbers of gamma H2AX nuclear foci remained high at 24 h, suggesting that some radiation-induced double-strand breaks remain unrepaired in the presence of iohexol. We established a mouse model of contrast-induced nephropathy, then showed that iohexol and ionizing radiation synergistically reduced renal function and induced doublestrand breaks. Importantly, iohexol induced significant macrophage accumulation and oxidative DNA damage in the kidneys of contrast-induced nephropathy model mice in the absence of ionizing radiation; these effects were amplified by ionizing radiation. The results suggest that underlying inflammation and oxidative DNA damage caused by iohexol contribute to the enhancement of radiation-induced doublestrand breaks, leading to contrast-induced nephropathy. (C) 2022 by Radiation Research Society