The utility of the minipig as an animal model in regulatory toxicology
The utility of the minipig as an animal model in regulatory toxicology
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DOI：
10.1016/j.vascn.2010.05.009
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发表时间：
2010-11-01
影响因子：
1.9
通讯作者：
Sims, Jennifer
中科院分区：
文献类型：
--
作者：
Bode, Gerd;Clausing, Peter;Sims, Jennifer
本文综述了小型猪作为动物模型在毒性试验中的应用价值。我们的审查是基于对小型猪的比较生物学的详细考虑，以及小型猪毒性试验的实际特点。小型猪作为非啮齿类动物毒理学模型，在与人的相似性以及对不同研究类型的适用性方面表现出有利的特征。一般毒理学研究可通过经口、经皮、胃肠外和吸入途径在小型猪中进行。对于生殖毒理学研究，小型猪作为非啮齿动物模型具有许多优势，尽管缺乏大分子的胎盘转移可能限制小型猪在生物技术产品生殖试验中的作用。对于安全药理学研究，小型猪是一种有利的模型，特别是在心血管系统方面。猪的免疫系统比狗的免疫系统更好地表征，使得猪成为基于免疫系统操纵的治疗方法的非人灵长类动物的有趣的替代模型。总体而言，该综述使我们相信小型猪可能是比犬更好的非啮齿类动物毒理学模型。然而，目前没有足够的比较数据来严格评价小型猪对人类药物诱导毒性的预测性，迫切需要研究提供实验数据来评价小型猪研究可能比传统非啮齿动物毒理学模型中进行的研究更好地反映人类药物诱导毒性的假设。更好地了解小型猪作为新生物制品安全性测试模型的潜在用途将具有特别的价值，其中小型猪可能在一些新产品的测试中取代非人灵长类动物的使用。(C)2010年爱思唯尔公司All rights reserved.
In this article we review the value and utility of the minipig as an animal model in regulatory toxicity testing. Our review is based on detailed consideration of the comparative biology of the minipig, and of the practical features of toxicity testing in the minipig. The minipig presents a favourable profile as a non-rodent toxicology model, in terms of the similarity to man and also in terms of applicability to different study types. Studies of general toxicology can be performed in the minipig by oral, cutaneous, parenteral and inhalation routes. For reproductive toxicology studies the minipig offers numerous advantages as a non-rodent model although the lack of placental transfer of macromolecules may limit the role of the minipig in reproductive testing of biotechnology products. For safety pharmacology studies the minipig is an advantageous model, particularly as regards the cardiovascular system. The immune system of the pig is better characterized than that of the dog, making the pig an interesting alternative model to the nonhuman primate for therapeutic approaches based on manipulation of the immune system. Overall, this review leads us to believe that the minipig might be a better non-rodent toxicology model than the dog. At the present time, however, insufficient comparative data is available to permit a rigorous evaluation of the predictivity of the minipig for human drug-induced toxicities and research is urgently needed to provide experimental data for evaluation of the hypothesis that minipig studies may better reflect human drug-induced toxicities than studies performed in traditional non-rodent toxicology models. It would be of particular value to gain a better vision of the potential utility of the minipig as a model for the safety testing of new biologics, where the minipig could potentially replace the use of non-human primates in the testing of some new products. (C) 2010 Elsevier Inc. All rights reserved.