Biomarkers of mitochondrial stress and DNA damage during pediatric catheter-directed neuroangiography – a prospective single-center study

IF 2.1 3区医学 Q2 PEDIATRICS

Pediatric Radiology Pub Date : 2024-09-17 DOI:10.1007/s00247-024-06048-7

Kaley A. Hogarth, Nicholas A. Shkumat, Simal Goman, Afsaneh Amirabadi, Suzanne Bickford, Prakash Muthusami, Bairbre L. Connolly, Jason T. Maynes

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Abstract

Background

Neuroangiography represents a critical diagnostic and therapeutic imaging modality whose associated radiation may be of concern in children. The availability of in vivo radiation damage markers would represent a key advancement for understanding radiation effects and aid in the development of radioprotective strategies.

Objective

Determine if biomarkers of cellular damage can be detected in the peripheral blood mononuclear cells (PBMC) of children undergoing neuroangiography.

Materials and methods

Prospective single-site study of 27 children. Blood collected pre and post neuroangiography, from which PBMC were isolated and assayed for biomarkers of mitochondrial stress (mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial DNA (mtDNA)) and DNA damage (γH2AX). Dose response of biomarkers vs. radiation dose was analyzed using linear regressions. The cohort was divided into higher (HD) and lower dose (LD) groups and analyzed using linear mixed models and compared using Welch’s t-tests.

Results

No biomarker exhibited a dose-dependent response following radiation (γH2AX: R² = 0.0012, P = 0.86; MMP: R² = 0.016, P = 0.53; mtDNA: R² = 0.10, P = 0.11; ROS: R² = 0.0023, P = 0.81). Groupwise comparisons showed no significant differences in γH2AX or ROS after radiation (γH2AX: LD: 0.6 ± 6.0, P = 0.92; HD: -7.5 ± 6.3 AU, P = 0.24; ROS: LD: 1.3 ± 2.8, P = 0.64; HD: -3.6 ± 3.0 AU, P = 0.24). Significant changes were observed to mitochondrial markers MMP (-53.7 ± 14.7 AU, P = 0.0014) and mtDNA (-1.1 ± 0.4 AU, P = 0.0092) for HD, but not the LD group (MMP: 26.1 ± 14.7 AU, P = 0.090; mtDNA: 0.2 ± 0.4, P = 0.65).

Conclusions

Biomarkers of mitochondrial stress in PBMC were identified during pediatric neuroangiography and warrant further investigation for radiation biodosimetry. However, isolating radiation-specific effects from those of procedural stress and general anesthesia requires further investigation.

Graphical Abstract

Abstract Image

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儿科导管引导神经血管造影过程中线粒体应激和DNA损伤的生物标志物--一项前瞻性单中心研究

背景神经血管造影术是一种重要的诊断和治疗成像方式，其相关辐射可能会对儿童造成影响。体内辐射损伤标记物的可用性是了解辐射效应的关键进步，有助于制定辐射防护策略。目的确定是否能在接受神经血管造影术的儿童的外周血单核细胞（PBMC）中检测到细胞损伤的生物标记物。在神经血管造影术前和术后采集血液，从中分离出外周血单核细胞，并检测线粒体应激（线粒体膜电位 (MMP)、活性氧 (ROS) 和线粒体 DNA (mtDNA)）和 DNA 损伤（γH2AX）的生物标志物。利用线性回归分析了生物标志物对辐射剂量的剂量反应。结果没有生物标志物在辐射后表现出剂量依赖性反应（γH2AX：R2 = 0.0012，P = 0.86；MMP：R2 = 0.016，P = 0.53；mtDNA：R2 = 0.10，P = 0.53）：R2=0.10，P=0.11；ROS：R2=0.0023，P=0.81）。分组比较显示，辐射后 γH2AX 或 ROS 无明显差异（γH2AX：LD：0.6 ± 6.0，P = 0.92；HD：-7.5 ± 6.3 AU，P = 0.24；ROS：LD：1.3 ± 2.0，P = 0.53；MtDNA：r2 = 0.10，P = 0.11；ROS：r2 = 0.0023，P = 0.81）：LD：1.3 ± 2.8，P = 0.64；HD：-3.6 ± 3.0 AU，P = 0.24）。在 HD 组，线粒体标记物 MMP（-53.7 ± 14.7 AU，P = 0.0014）和 mtDNA（-1.1 ± 0.4 AU，P = 0.0092）发生了显著变化，而在 LD 组则没有（MMP：26.1 ± 14.7 AU，P = 0.结论在小儿神经血管造影过程中发现了 PBMC 线粒体应激的生物标志物，值得进一步研究用于辐射生物模拟。然而，将辐射特异性效应从程序应激和全身麻醉的效应中分离出来还需要进一步研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Radiology 医学-核医学

CiteScore

4.40

自引率

17.40%

发文量

300

审稿时长

3-6 weeks

期刊介绍： Official Journal of the European Society of Pediatric Radiology, the Society for Pediatric Radiology and the Asian and Oceanic Society for Pediatric Radiology Pediatric Radiology informs its readers of new findings and progress in all areas of pediatric imaging and in related fields. This is achieved by a blend of original papers, complemented by reviews that set out the present state of knowledge in a particular area of the specialty or summarize specific topics in which discussion has led to clear conclusions. Advances in technology, methodology, apparatus and auxiliary equipment are presented, and modifications of standard techniques are described. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.