Department of Animal Protection, Welfare and Behaviour, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackeho tr. 1946/1, 612 42, Brno, Czech Republic.
Department of Immunology, Veterinary Research Institute, Hudcova 296/70, 621 00, Brno, Czech Republic.
Environ Sci Pollut Res Int. 2020 Jan;27(2):1686-1696. doi: 10.1007/s11356-019-06726-2. Epub 2019 Nov 21.
The effect of venlafaxine, a pharmaceutical commonly found in aquatic environment, was analyzed on non-target organism, Danio rerio (Hamilton, 1822). D. rerio embryos were treated by two different concentrations of venlafaxine: either concentration relevant in aquatic environment (0.3 μg/L) or concentration that was two orders of magnitude higher (30 μg/L) for the evaluation of dose-dependent effect. Time-dependent effect was rated at 24, 96, and 144 h post-fertilization (hpf). For gene expression, genes representing one of the phases of xenobiotic biotransformation (0 to III) were selected. The results of this study showed that the effect of venlafaxine on the zebrafish embryos is the most evident at hatching (96 hpf). At this time, the results showed a downregulation of gene expression in each phase of biotransformation and in both tested concentrations. In contrast, an upregulation of most of the genes was observed 144 hpf for both tested venlafaxine concentrations. The study shows that venlafaxine can affect the gene expression of biotransformation enzymes in D. rerio embryos even in the environmentally relevant concentration and thus disrupt the process of biotransformation. Moreover, the pxr regulation of genes seems to be disrupted after venlafaxine exposure in dose- and time-dependent manner.
研究分析了在水生环境中常见的药物文拉法辛对非目标生物斑马鱼(Danio rerio (Hamilton, 1822))的影响。研究采用两种不同浓度的文拉法辛处理斑马鱼胚胎:一种是与水生环境相关的浓度(0.3μg/L),另一种是浓度高出两个数量级(30μg/L),以评估剂量依赖性效应。时间依赖性效应在受精后 24、96 和 144 小时(hpf)进行评估。为了进行基因表达分析,选择了代表生物转化(0 到 III 期)一个阶段的基因。研究结果表明,文拉法辛对斑马鱼胚胎的影响在孵化时(96 hpf)最为明显。此时,研究结果显示各生物转化阶段的基因表达均下调,且在两种测试浓度下均如此。相比之下,在两种测试浓度下,144 hpf 时大多数基因的表达均上调。研究表明,文拉法辛即使在环境相关浓度下也会影响斑马鱼胚胎中生物转化酶的基因表达,从而破坏生物转化过程。此外,pxr 对基因的调控似乎在文拉法辛暴露后呈现出剂量和时间依赖性的破坏。