Kocour Kroupová Hana, Steinbach Christoph, Pech Michal, Šauer Pavel, Prokopová Ilona, Grabic Roman, Brooks Bryan W, Grabicová Kateřina
University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zátiší 728/II, 389 25, Vodňany, Czech Republic.
Institute of Hydrodynamics of the Czech Academy of Sciences, Pod Patankou 30/5, 160 00 Prague 6, Czech Republic.
Environ Pollut. 2025 Jul 30;384:126922. doi: 10.1016/j.envpol.2025.126922.
Though bioconcentration of ionizable pharmaceuticals has received increased attention in fish and invertebrates, an understanding of bioconcentration of these contaminants of emerging concern by amphibians is lacking. Here, we investigated the bioconcentration, elimination and metabolism of a model weak base, the antihistamine diphenhydramine (DPH), at different developmental stages in the African clawed frog (Xenopus laevis), a well-established amphibian model. These developmental stages of X. laevis included tadpoles at pre-metamorphic stages (NF 49-52), tadpoles at pro-metamorphic and climax stages (NF 56-60) and newly metamorphosed frogs (NF 66). During metamorphosis from tadpoles to frogs, significant structural and functional changes occur in X. laevis, affecting respiration (gill resorption and lung development), feeding, digestion and skin structure. Animals were exposed to 10 μg/L DPH for 96 h, a concentration that did not affect mortality, development, growth, or behaviour, and then transferred to DPH-free water for 72 h. Relatively low steady-state bioconcentration factors (BCF) of DPH were determined, ranging from 21 to 36; kinetic BCF (BCF) values ranged from 26 to 161. The depuration half-life (t) and 95 % loss in the depuration phase (t) of DPH were 19 and 20 h, and 83 and 85 h in pre-metamorphic and pro-metamorphic tadpoles, respectively. DPH had an approximately three times longer t (66 h) and a t (283 h) in juvenile frogs, suggesting differences in excretion and/or metabolism with age. Using non-targeted screening, DPH-N-oxide and DPH-N-desmethyl were identified at Schymanski level 2 as the exclusive DPH metabolites in all stages of X. laevis examined, indicating a major difference in the metabolism of DPH in frogs compared to other animals and humans. To our knowledge, this study provides initial observations for bioconcentration, elimination, and metabolism of an ionizable pharmaceutical in amphibians.
尽管可离子化药物在鱼类和无脊椎动物中的生物富集已受到越来越多的关注，但对于两栖动物对这些新出现的关注污染物的生物富集情况仍缺乏了解。在此，我们研究了一种典型弱碱——抗组胺药苯海拉明（DPH）在非洲爪蟾（非洲爪蟾，一种成熟的两栖动物模型）不同发育阶段的生物富集、消除和代谢情况。非洲爪蟾的这些发育阶段包括变态前阶段的蝌蚪（NF 49 - 52）、变态前期和高峰期的蝌蚪（NF 56 - 60）以及刚变态的幼蛙（NF 66）。在从蝌蚪变态为青蛙的过程中，非洲爪蟾会发生显著的结构和功能变化，影响呼吸（鳃吸收和肺发育）、摄食、消化和皮肤结构。将动物暴露于10μg/L的DPH中96小时，该浓度不影响死亡率、发育、生长或行为，然后转移到不含DPH的水中72小时。测定了DPH相对较低的稳态生物富集因子（BCF），范围为21至36；动力学BCF（BCF）值范围为26至161。DPH在变态前和变态前期蝌蚪中的净化半衰期（t）和净化阶段95%的损失时间（t）分别为19小时和20小时，以及83小时和85小时。DPH在幼蛙中的t（66小时）和t（283小时）大约长三倍，表明排泄和/或代谢随年龄存在差异。通过非靶向筛选，在所有检测的非洲爪蟾阶段中，DPH - N - 氧化物和DPH - N - 去甲基化物在Schymanski水平2被鉴定为唯一的DPH代谢物，这表明与其他动物和人类相比，青蛙中DPH的代谢存在重大差异。据我们所知，本研究为两栖动物中可离子化药物的生物富集、消除和代谢提供了初步观察结果。
