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The importance of pH: How aquarium water is affecting behavioural responses to drug exposure in larval zebrafish

机译:pH值的重要性:水族馆水如何影响幼虫斑马鱼在药物暴露中的行为反应

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There has been rapid growth in the use of larval zebrafish as a complementary vertebrate model for drug discovery, abuse liability and pharmacological toxicology, resulting in a huge increase in zebrafish facilities worldwide. However, many research groups working with zebrafish do not typically report the pH of husbandry conditions in methodologies, nor are the pH of drug treatments reported in many research articles. This unknown factor can be a major contributor in the differential effects of drug treatments. Therefore, as a case study, we tested the impact of altering pH of several drugs of abuse and assessed locomotor changes associated with a single drug concentration delivered at different pHs. We found that a change of a single pH unit, within the pH ranges commonly used in zebrafish husbandry, was enough to alter locomotor activity at a fixed drug concentration. Many pharmacological agents are dependent on environmental factors, such as pH, to determine bioavailability. Efficaciousness for many classes of drug is dependent on their ionization state in which shifts towards uncharged species can influence the easy of a drug crossing biological membranes. Thus, we urge users to report pH in husbandry methods and drug treatments to improve replicability and inter-study comparisons.
机译:作为药物发现、滥用责任和药理学毒理学的补充脊椎动物模型,斑马鱼幼虫的使用迅速增长,导致世界范围内斑马鱼设施的大幅增加。然而,许多研究斑马鱼的研究小组通常不会在方法中报告养殖条件的pH值,许多研究文章也没有报告药物治疗的pH值。这一未知因素可能是药物治疗效果差异的主要因素。因此,作为一个案例研究,我们测试了改变几种滥用药物pH值的影响,并评估了在不同pH值下与单一药物浓度相关的运动变化。我们发现,在斑马鱼养殖中常用的pH范围内,单个pH单位的变化足以改变固定药物浓度下的运动活性。许多药物依赖于环境因素,如pH值来确定生物利用度。许多种类药物的有效性取决于它们的电离状态,在这种电离状态下,向不带电物种的转移会影响药物穿过生物膜的容易程度。因此,我们敦促用户报告饲养方法和药物治疗中的pH值,以提高可复制性和研究间比较。

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