以秀丽隐杆线虫为模式生物评价抗癌药物的神经毒性。

IF 1.8 4区 医学 Q4 TOXICOLOGY
Yuko Sakaguchi, Marin Mizukami, Yamashiro Hiroka, Kayuko Miyasaka, Kyoko Niwa, Koji Arizono, Nobuhiro Ichikawa
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引用次数: 1

摘要

基于铂的药物,包括奥沙利铂(L-OHP)和顺铂(CDDP),以及微管抑制剂紫杉醇(PTX)和长春新碱(VCR),与化疗诱导的周围神经病变(CIPN)相关。在这项研究中,我们检测并比较了L-OHP、CDDP、PTX和VCR诱导的神经病变的特征,以评估秀丽隐杆线虫(C. elegans)是否可以作为人类CIPN的模式生物。线虫在线虫生长培养基上培养,采用凝胶过滤同步L1幼虫。然后我们进行了生物测定并检查了运动性。在运动测试中,暴露时间分别为2小时、24小时和48小时,并测量每次暴露时间和终止暴露后24小时的时间依赖性效应。我们观察到L-OHP和CDDP在一定浓度以上具有浓度依赖效应,PTX和VCR在生物测定中具有浓度依赖的负作用。在终止暴露后,L-OHP-、PTX-和vcr处理的蠕虫运动能力恢复。然而,即使在终止暴露24小时后,CDDP暴露仍有降低运动性的趋势。L-OHP暴露后2小时运动能力下降,停药后24小时有恢复趋势。本研究结果表明秀丽隐杆线虫可能表现出与人类相似的神经病变特征,表明该生物可能是探索人类CIPN的合适模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of neurotoxicity of anticancer drugs using nematode Caenorhabditis elegans as a model organism.

It is well established that platinum-based drugs, including oxaliplatin (L-OHP) and cisplatin (CDDP), as well as microtubule inhibitors paclitaxel (PTX) and vincristine (VCR), are associated with chemotherapy-induced peripheral neuropathy (CIPN). In this study, we examined and compared the characteristics of neuropathies induced by L-OHP, CDDP, PTX, and VCR to evaluate whether Caenorhabditis elegans (C. elegans) could serve as a model organism for human CIPN. Worms were cultured on nematode growth medium plates, and L1 larvae synchronized by gel filtration were employed. We then performed bioassays and examined motility. In the motility test, exposure was performed for 2, 24, and 48 hr, and time-dependent effects were measured for each exposure time and 24 hr after terminating exposure. Herein, we observed that L-OHP and CDDP exerted concentration-dependent effects above a certain concentration, and PTX and VCR exerted concentration-dependent negative effects in the bioassay. Motility recovered in L-OHP-, PTX-, and VCR-treated worms on terminating exposure. However, CDDP exposure tended to reduce motility even 24 hr after terminating exposure. L-OHP exposure could decrease motility 2 hr after exposure, with a trend toward recovery 24 hr after terminating drug exposure. The findings of the present study revealed that C. elegans could exhibit neuropathy characteristics suggested to be similar to those observed in humans, indicating that this organism could be a suitable model to explore human CIPN.

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来源期刊
CiteScore
3.20
自引率
5.00%
发文量
53
审稿时长
4-8 weeks
期刊介绍: The Journal of Toxicological Sciences (J. Toxicol. Sci.) is a scientific journal that publishes research about the mechanisms and significance of the toxicity of substances, such as drugs, food additives, food contaminants and environmental pollutants. Papers on the toxicities and effects of extracts and mixtures containing unidentified compounds cannot be accepted as a general rule.
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