Developmental toxicity of diclofenac and elucidation of gene regulation in zebrafish (Danio rerio).
Environmental pollution by emerging contaminants, e.g. pharmaceuticals, has become a matter of widespread concern in recent years. We investigated the membrane transport of diclofenac and its toxic effects on gene expression and the development of zebrafish embryos. The association of diclofenac with the embryos conformed to the general partition model at low concentration, the partition coefficient being 0.0033 ml per embryo. At high concentration, the interaction fitted the Freundlich model. Most of the diclofenac remained in the extracellular aqueous solution with less than 5% interacting with the embryo, about half of which was adsorbed on the membranes while the rest entered the cytoplasm. Concentrations of diclofenac over 10.13 μM were lethal to all the embryos, while 3.78 μM diclofenac was teratogenic. The development abnormalities at 4 day post treatment (dpt) include shorter body length, smaller eye, pericardial and body edema, lack of liver, intestine and circulation, muscle degeneration, and abnormal pigmentation. The portion of the diclofenac transferred into the embryo altered the expression of certain genes, e.g. down-regulation of Wnt3a and Gata4 and up-regulation of Wnt8a. The alteration of expression of such genes or the regulation of downstream genes could cause defects in the cardiovascular and nervous systems.
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Jia-Bin
JB
Chen
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Hong-Wen
HW
Gao
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Ya-Lei
YL
Zhang
Hunter Biotechnology, Inc., Hangzhou, 311231, China.
Yong
Y
Zhang
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Xue-Fei
XF
Zhou
Hunter Biotechnology, Inc., Hangzhou, 311231, China.
Chun-Qi
CQ
Li
State Key Laboratory of Pollution Control and Resources Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai, 200092, China.
Hai-Ping
HP
Gao
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D004008:Diclofenac / Q000633:toxicity*; D054750:Ecotoxicology; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects*; D013997:Time Factors; D015027:Zebrafish / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004785:Environmental Pollutants; D004008:Diclofenac