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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01457

Psoralen induces developmental toxicity in zebrafish embryos/larvae through oxidative stress, apoptosis and energy metabolism disorder

 Qing Xia1*, Lingying Wei1,  Yun Zhang1, Haotian Kong1, Yongping Shi1, 2,  Xue Wang1, xiqiang Chen1, Liwen Han1 and Kechun Liu1
  • 1Shandong Academy of Sciences, China
  • 2Shanxi Medical University, China

Psoralen toxicity is an issue of wide concern. However, an assay for psoralen-induced developmental toxicity has not been reported to date. Moreover, the underlying mechanism of psoralen-induced developmental toxicity is unclear. Therefore, this study attempted to develop a psoralen-induced developmental toxicity assay in zebrafish embryos/larvae. Psoralen treatment caused a decrease in the hatching rate and body length and a significant increase in the malformation rate of zebrafish. Yolk retention, pericardial edema, swim-bladder deficiency, and curved body shape were also observed after psoralen treatment. Yolk retention might have been caused by an abnormality in lipid metabolism. Further experiments indicated that psoralen exerted toxic effects on the developing heart, liver, macrophages, and nervous system. Increased generation of reactive oxygen species, inhibition of total superoxide dismutase activity, and increased malondialdehyde concentrations indicated inhibition of antioxidant capacity and the presence of oxidative stress. A greater number of apoptotic cells were observed after psoralen exposure, relative to the control. Furthermore, the results of gene-expression analysis showed that psoralen induced developmental toxicity by means of oxidative stress, apoptosis, and energy metabolism abnormalities. These findings will be helpful in understanding psoralen-induced toxicity.

Keywords: Energy metabolism disorder, Apoptosis, Oxidative Stress, developmental toxicity, Zebrafish, Psoralen

Received: 13 Sep 2018; Accepted: 29 Nov 2018.

Edited by:

Salvatore Salomone, Università degli Studi di Catania, Italy

Reviewed by:

Patrizia Ferretti, University College London, United Kingdom
Claure Nain Lunardi, Universidade de Brasília, Brazil  

Copyright: © 2018 Xia, Wei, Zhang, Kong, Shi, Wang, Chen, Han and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Qing Xia, Shandong Academy of Sciences, Jinan, Shandong Province, China,