Evaluation of infliximab-induced genotoxicity and possible action on BCL-2 and P53 genes.

IF 2.3 4区 医学 Q3 ENVIRONMENTAL SCIENCES Journal of Toxicology and Environmental Health-Part A-Current Issues Pub Date : 2024-09-16 Epub Date: 2024-06-26 DOI:10.1080/15287394.2024.2368619
Murillo de Sousa Pinto, Luiz Guilherme Oliveira Fontoura, Isabela da Rosa Borges, Abel Vieira de Melo Bisneto, Geyciane Rosa de Oliveira, Lílian Carla Carneiro, Lee Chen Chen, Aroldo Vieira de Moraes Filho
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Abstract

Although the last pandemic created an urgency for development of vaccines, there was a continuous and concerted effort to search for therapeutic medications among existing drugs with different indications. One of the medications of interest that underwent this change was infliximab (IFM). This drug is used as an anti-inflammatory, predominantly in patients with Crohn 's disease, colitis ulcerative, and rheumatoid arthritis. In addition to these patients, individuals infected with Coronavirus Disease (COVID-19) were administered this chimeric monoclonal antibody (IMF) to act as an immunomodulator for patients in the absence of comprehensive research. Consequently, the present study aimed to examine the genotoxic effects attributed to IFM treatment employing different assays in vivo using mouse Mus musculus. Therefore, IFM was found to induce genotoxic effects as evidenced by the comet assay but did not demonstrate genotoxic potential utilizing mouse bone marrow MN test. The results of evaluating the expression of the P53 and BCL-2 genes using RT-qPCR showed stimulation of expression of these genes at 24 hr followed by a decline at 48 hr. Although the comet assay provided positive results, it is noteworthy that based upon negative findings in the micronucleus test, the data did not demonstrate significant changes in the genetic material that might affect the therapeutic use of IFM. The stimulation of expression of P53 and BCL-2 genes at 24 hr followed by a decline at 48 hr suggest a transient, if any, effect on genetic material. However, there is still a need for more research to more comprehensively understand the genotoxic profile of this medication.

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评估英夫利昔单抗诱导的基因毒性以及对 BCL-2 和 P53 基因的可能作用。
尽管上一次大流行造成了开发疫苗的紧迫性,但人们仍在不断共同努力,从现有的不同适应症药物中寻找治疗药物。英夫利昔单抗(IFM)就是经历了这种变化的药物之一。这种药物主要用于克罗恩病、溃疡性结肠炎和类风湿性关节炎患者的抗炎治疗。除这些患者外,感染了冠状病毒病(COVID-19)的患者也被注射了这种嵌合单克隆抗体(IMF),在缺乏全面研究的情况下,该药可作为患者的免疫调节剂。因此,本研究以小鼠麝香为研究对象,采用不同的试验方法,在体内检测 IFM 治疗的基因毒性效应。因此,通过彗星试验发现 IFM 可诱导基因毒性效应,但利用小鼠骨髓 MN 试验则未显示出基因毒性潜力。使用 RT-qPCR 评估 P53 和 BCL-2 基因表达的结果显示,这些基因的表达在 24 小时内受到刺激,随后在 48 小时内下降。虽然彗星试验得出了阳性结果,但值得注意的是,根据微核试验的阴性结果,数据并未显示遗传物质发生了可能影响 IFM 治疗用途的重大变化。P53 和 BCL-2 基因的表达在 24 小时内受到刺激,随后在 48 小时内下降,这表明对遗传物质的影响是短暂的(如果有的话)。不过,仍有必要开展更多研究,以更全面地了解这种药物的遗传毒性特征。
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来源期刊
CiteScore
5.20
自引率
19.20%
发文量
46
审稿时长
8-16 weeks
期刊介绍: The Journal of Toxicology and Environmental Health, Part A , Current Issues is an authoritative journal that features strictly refereed original research in the field of environmental sciences, public and occupational health, and toxicology.
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