The zebrafish (Danio rerio) embryo has increasingly been used as an alternative model in human and environmental toxicology. Since the cytochrome P450 (CYP) system is of fundamental importance for the understanding and correct interpretation of the outcome of toxicological studies, constitutive and xenobiotic-induced 7-methoxycoumarin-O-demethylase (MCOD), i.e. ‘mammalian CYP2-like’, activities were monitored in vivo in zebrafish embryos via confocal laser scanning microscopy. In order to elucidate molecular mechanisms underlying the MCOD induction, dose-dependent effects of the prototypical CYP inducers β-naphthoflavone (aryl hydrocarbon receptor (AhR) agonist), rifampicin (pregnane X receptor (PXR) agonist), carbamazepine and phenobarbital (constitutive androstane receptor (CAR) agonists) were analyzed in zebrafish embryos of varying age.

Starting from 36 h of age, all embryonic stages of zebrafish could be shown to have constitutive MCOD activity, albeit with spatial variation and at distinct levels. Whereas carbamazepine, phenobarbital and rifampicin had no effect on in vivo MCOD activity in 96 h old zebrafish embryos, the model aryl hydrocarbon receptor agonist β-naphthoflavone significantly induced MCOD activity in 96 h old zebrafish embryos at 46–734 nM, however, without a clear concentration-effect relationship. Induction of MCOD activity by β-naphthoflavone gradually decreased with progression of embryonic development. By in vivo characterization of constitutive and xenobiotic-induced MCOD activity patterns in 36, 60, 84 and 108 h old zebrafish embryos, this decrease could primarily be attributed to an age-related decline in the induction of MCOD activity in the cardiovascular system. Results of this study provide novel insights into the mechanism and extent, by which specific CYP activities in early life-stages of zebrafish can be influenced by exposure to xenobiotics. The study thus lends further support to the view that zebrafish embryos– at least from an age of 36 h – have an elaborate and inducible biotransformation system.

斑马鱼（Danio rerio）胚胎已越来越多地用作人类和环境毒理学的替代模型。由于细胞色素P450（CYP）系统对于理解和正确解释毒理学研究结果至关重要，因此组成型和异种生物诱导的7-甲氧基香豆素-O-脱甲基酶（MCOD）（即``哺乳动物CYP2样''）的活动通过斑马鱼胚胎体内监测共聚焦激光扫描显微镜。为了阐明MCOD诱导的分子机制，典型的CYP诱导剂β-萘黄酮（芳烃受体（AhR）激动剂），利福平（孕烷X受体（PXR）激动剂），卡马西平和苯巴比妥（组成型雄甾烷）的剂量依赖性作用受体（CAR）激动剂）在不同年龄的斑马鱼胚胎中进行了分析。

从36小时龄开始，斑马鱼的所有胚胎阶段都可以显示出本构MCOD活性，尽管存在空间差异并且水平不同。卡马西平，苯巴比妥和利福平对96 h老斑马鱼胚胎的体内MCOD活性没有影响，而模型芳烃受体激动剂β-萘黄酮在46–734 nM时可显着诱导96 h老斑马鱼胚胎的MCOD活性。明确的浓度效应关系。β-萘黄酮对MCOD活性的诱导随着胚胎发育的进程逐渐降低。通过体内表征36、60、84和108 h老斑马鱼胚胎中本构和异种生物诱导的MCOD活性模式，这种下降可能主要归因于心血管系统中与年龄相关的MCOD活性下降。这项研究的结果提供了有关机制和程度的新见解，通过这些机制和程度，斑马鱼生命早期的特定CYP活性可以受到异源生物的影响。因此，这项研究进一步支持了斑马鱼胚胎（至少从36小时开始）具有复杂且可诱导的生物转化系统的观点。