The evaluation of oxidative damage of DNA after poisoning with nerve agents.

IF 2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Journal of applied biomedicine Pub Date : 2019-12-01 Epub Date: 2019-11-13 DOI:10.32725/jab.2019.017

Jiri Kassa, Rudolf Stetina

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引用次数: 1

Abstract

The potency of three nerve agents (sarin, soman, tabun) to induce oxidative damage of DNA in lymphocytes, liver and brain during lethal or sublethal poisoning was investigated. The single strand breaks or oxidative base DNA damage was evaluated with the help of Comet assay and a specific enzyme able to detect oxidative bases of DNA (endonuclease III). While sarin and soman administered at sublethal doses corresponding to 50% of their LD50 values were not able to induce oxidative damage of DNA, their lethal dose (LD50) induced the significant increase of the number of oxidative bases in DNA of hepatocytes. In addition, tabun administered at lethal dose (LD50) induced significant increase of the number of single strand breaks and oxidative bases of DNA in glial cells isolated from pontomedullar brain region. Thus, some nerve agents were able to induce oxidative damage in the peripheral as well as central compartment but only in the case of severe poisoning caused by lethal doses of nerve agents. This non-cholinergic effect of nerve agents has probably consequences with nerve agents-induced hypoxic status during acute cholinergic crisis and it can contribute to their long-term toxic effects.

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神经毒剂中毒后DNA氧化损伤的评价。

研究了三种神经毒剂(沙林、索曼、塔本)在致死性或亚致死性中毒过程中对淋巴细胞、肝脏和脑DNA的氧化损伤作用。单链断裂或DNA氧化碱基损伤用彗星测定法和一种能够检测DNA氧化碱基的特异性酶(核酸内切酶III)来评估。虽然沙林和索曼在其LD50值的50%的亚致死剂量下不能诱导DNA氧化损伤，但其致死剂量(LD50)诱导肝细胞DNA氧化碱基数量显著增加。此外，致死剂量(LD50)给药的他奔诱导桥脑区分离的神经胶质细胞单链断裂数量和DNA氧化碱基显著增加。因此，一些神经毒剂能够诱导外周和中央隔室的氧化损伤，但只有在致命剂量的神经毒剂引起严重中毒的情况下。神经毒剂的这种非胆碱能作用可能导致急性胆碱能危机时神经毒剂引起的缺氧状态，并可能导致其长期毒性作用。

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

Journal of applied biomedicine PHARMACOLOGY & PHARMACY-

CiteScore

2.40

自引率

7.70%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Applied Biomedicine promotes translation of basic biomedical research into clinical investigation, conversion of clinical evidence into practice in all medical fields, and publication of new ideas for conquering human health problems across disciplines. Providing a unique perspective, this international journal publishes peer-reviewed original papers and reviews offering a sensible transfer of basic research to applied clinical medicine. Journal of Applied Biomedicine covers the latest developments in various fields of biomedicine with special attention to cardiology and cardiovascular diseases, genetics, immunology, environmental health, toxicology, neurology and oncology as well as multidisciplinary studies. The views of experts on current advances in nanotechnology and molecular/cell biology will be also considered for publication as long as they have a direct clinical impact on human health. The journal does not accept basic science research or research without significant clinical implications. Manuscripts with innovative ideas and approaches that bridge different fields and show clear perspectives for clinical applications are considered with top priority.