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鱼类及其他非哺乳动物哨兵物种免疫毒性的生物标志物:对哺乳动物的预测价值?

Biomarkers of immunotoxicity in fish and other non-mammalian sentinel species: predictive value for mammals?

作者信息

Zelikoff J T

机构信息

New York University School of Medicine, Department of Environmental Medicine, NY 10987, USA.

出版信息

Toxicology. 1998 Aug 7;129(1):63-71. doi: 10.1016/s0300-483x(98)00064-x.

DOI:10.1016/s0300-483x(98)00064-x
PMID:9769111
Abstract

Through the efforts of different laboratories, a battery of immunological assays is available to predict the immunotoxicity of xenobiotics. These assays, originally developed in rodents, have been adapted for use in a variety of animal species and are now used routinely in these models to assess the immunotoxicity of different chemical classes. For example, our laboratory has employed assays that measure antibody-forming cell response to T-dependent antigens, T- and B-cell lymphoproliferation, macrophage function, and host resistance against infectious bacteria to assess metal-induced immunotoxicity in laboratory-reared Japanese medaka (Oryzias latipes); immunologically-related assays measuring antioxidant activity have also been used in this capacity. Results of the aforementioned investigations have shown the usefulness of these endpoints to reliably demonstrate chemical-mediated immunotoxicity in teleost systems. Many of these same endpoints have also proved successful for predicting the immunotoxic effects of contaminated aquatic environments in feral fish populations. For example, smallmouth bass collected from a chlorinated hydrocarbon-contaminated site demonstrated significant changes in blood cell profiles and kidney phagocyte function compared to fish collected from a 'clean water' reference site. Some of these same immune parameters have also been used successfully to predict the immunotoxicity of polluted aquatic environments in feral populations of fish-eating birds and harbor seals. While interspecies extrapolation is difficult and should be approached with caution due to variables such as metabolism and pharmacokinetics, results from these studies demonstrate the usefulness of these immune assays to predict the immunomodulating effects of xenobiotics in fish and other wildlife species, as well as the applicability of fish to serve as additional/alternate animal models for mammalian species in immunotoxicological studies.

摘要

通过不同实验室的努力,现已拥有一系列免疫分析方法来预测外源性物质的免疫毒性。这些分析方法最初是在啮齿动物中开发的,现已适用于多种动物物种,目前经常用于这些模型中,以评估不同化学类别的免疫毒性。例如,我们实验室采用了测量对T细胞依赖性抗原的抗体形成细胞反应、T细胞和B细胞淋巴细胞增殖、巨噬细胞功能以及宿主对感染性细菌的抵抗力的分析方法,来评估实验室饲养的日本青鳉(Oryzias latipes)中金属诱导的免疫毒性;测量抗氧化活性的免疫相关分析方法也已用于此目的。上述研究结果表明,这些终点对于可靠地证明硬骨鱼系统中化学介导的免疫毒性是有用的。许多相同的终点也已成功用于预测野生鱼类种群中受污染水生环境的免疫毒性影响。例如,与从“清洁水”参考地点采集的鱼类相比,从受氯代烃污染地点采集的小口黑鲈在血细胞谱和肾脏吞噬细胞功能方面表现出显著变化。其中一些相同的免疫参数也已成功用于预测食鱼鸟类和斑海豹野生种群中污染水生环境的免疫毒性。虽然由于代谢和药代动力学等变量,种间外推很困难且应谨慎进行,但这些研究结果表明,这些免疫分析方法对于预测外源性物质对鱼类和其他野生动物物种的免疫调节作用是有用的,以及鱼类作为免疫毒理学研究中哺乳动物物种的额外/替代动物模型的适用性。

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