Chakravarthy Sridhara, Sadagopan Sathish, Nair Ayyappan, Sukumaran Sunil Kumar
Discovery Biology, Anthem Biosciences Private Limited , Bangalore, India .
Zebrafish. 2014 Apr;11(2):154-66. doi: 10.1089/zeb.2013.0924. Epub 2014 Jan 15.
Compounds routinely used to increase the quality of life and combat disease undergo stringent potency and biosafety tests before approval. However, based on the outcome of ongoing research, new norms need to be effected to ensure that the compounds conform to biosafety at all target levels of activity. Whereas in vitro tests used to assess biosafety lack the potency and the translational attribute of a whole animal, mammalian preclinical models are expensive and time exhaustive. Zebrafish (Danio rerio) has emerged as an attractive alternative for biosafety studies due to its small size, genetics, breeding capabilities, and most importantly, similarity at the molecular and physiological levels with humans. It has been used extensively for testing various forms of toxicity, including developmental toxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We review here the utility of zebrafish as a powerful, sensitive, quantitative, noninvasive, and high-throughput whole-animal assay to screen for toxicity. Different forms of toxicity will be discussed briefly before we highlight the present state of genotoxicity study in zebrafish. This review, a first in this research area, will serve as a comprehensive introduction to the field of genotoxicity assay using zebrafish, a nascent but promising field that assays compounds for DNA damage. We also discuss possible approaches that could potentially be pursued to overcome some of the shortcomings in current genotoxic studies.
通常用于提高生活质量和对抗疾病的化合物在获批之前要经过严格的效力和生物安全性测试。然而,根据正在进行的研究结果,需要制定新的规范,以确保这些化合物在所有目标活性水平上都符合生物安全性。用于评估生物安全性的体外测试缺乏完整动物的效力和转化特性,而哺乳动物临床前模型成本高昂且耗时费力。斑马鱼(Danio rerio)因其体型小、具有遗传学特征、繁殖能力强,以及最重要的是在分子和生理水平上与人类相似,已成为生物安全性研究中一种有吸引力的替代选择。它已被广泛用于测试各种形式的毒性,包括发育毒性、心脏毒性、肾毒性和肝毒性。我们在此回顾斑马鱼作为一种强大、灵敏、定量、非侵入性且高通量的整体动物检测方法用于筛选毒性的效用。在突出斑马鱼遗传毒性研究的现状之前,将简要讨论不同形式的毒性。这篇综述是该研究领域的首篇综述,将作为对使用斑马鱼进行遗传毒性检测领域的全面介绍,这是一个新兴但很有前景的领域,用于检测化合物对DNA的损伤。我们还将讨论可能采取的方法,以克服当前遗传毒性研究中的一些缺点。