Gao Yongfei, Feng Jianfeng, Wang Cancan, Zhu Lin
Key Laboratory of Pollution Process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
Key Laboratory of Pollution Process and Environmental Criteria of Ministry of Education and Tianjin Key Laboratory of Environmental Remediation and Pollution Control, College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China.
Ecotoxicol Environ Saf. 2017 Apr;138:146-153. doi: 10.1016/j.ecoenv.2016.12.028. Epub 2016 Dec 30.
Quantitative predictions of metal-metal interactions and toxicity in aquatic organisms meet a unique challenge. Accumulation and toxicity of Cu and Zn mixtures in zebrafish larvae has been quantified in binary metal system with variable combinatorial concentrations in order to understand the interactions between essential trace metals and assess availability of the toxicokinetic-toxicodynamic (TK-TD) model which simulated the uptake of metals over time as well as metal toxicity after 24h of exposure. Competitive uptake experiments showed a straightforward antagonistic competition, as would be predicted by Michaelis-Menten competitive equilibrium model. Zn uptake decreased significantly in the presence of Cu concentrations higher than 10M. Cu was shown to compete strongly with Zn for uptake, having a higher affinity constant to biotic ligand (BL) sites (K=10M) than Zn (K=10M). TK-TD model considering potential metal-metal antagonism interactions showed good predictive power in predicting accumulation and toxicity of Cu-Zn mixtures in zebrafish larvae with the high coefficient of determination (r) and significant level (p). In particular, with the elevated Zn concentrations in mixtures, the TD model showed better predictive power in predicting toxicity of 10M Cu concentration in Cu-Zn mixtures. The TK-TD analysis provided some new insights into the interactive mechanism of binary Cu and Zn exposure in aquatic animals and may have important implications for our understanding of quantitative predictions of metal-metal interactions and toxicity in a field where animals are simultaneously exposed to several metals.
对水生生物中金属-金属相互作用和毒性进行定量预测面临着独特的挑战。为了了解必需微量元素之间的相互作用，并评估毒代动力学-毒效动力学（TK-TD）模型的适用性，该模型模拟了金属随时间的吸收以及暴露24小时后的金属毒性，在具有可变组合浓度的二元金属系统中对斑马鱼幼体中铜和锌混合物的积累和毒性进行了量化。竞争性吸收实验显示出直接的拮抗竞争，正如米氏竞争平衡模型所预测的那样。在铜浓度高于10μM的情况下，锌的吸收显著下降。结果表明，铜与锌在吸收过程中存在强烈竞争，其对生物配体（BL）位点的亲和常数（K = 10μM）高于锌（K = 10μM）。考虑到潜在金属-金属拮抗相互作用的TK-TD模型在预测斑马鱼幼体中铜-锌混合物的积累和毒性方面具有良好的预测能力，决定系数（r）高且显著水平（p）。特别是，随着混合物中锌浓度的升高，TD模型在预测铜-锌混合物中10μM铜浓度的毒性方面表现出更好的预测能力。TK-TD分析为水生动物中二元铜和锌暴露的相互作用机制提供了一些新的见解，可能对我们理解动物同时暴露于多种金属的领域中金属-金属相互作用和毒性的定量预测具有重要意义。
