Xia Qing, Wei Lingying, Zhang Yun, Kong Haotian, Shi Yongping, Wang Xue, Chen Xiqiang, Han Liwen, Liu Kechun
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
School of Pharmacy, Shanxi Medical University, Taiyuan, China.
Front Pharmacol. 2018 Dec 18;9:1457. doi: 10.3389/fphar.2018.01457. eCollection 2018.
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, phagocytes, 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.
补骨脂素毒性是一个广受关注的问题。然而，迄今为止尚未见有关补骨脂素诱导发育毒性的检测方法的报道。此外，补骨脂素诱导发育毒性的潜在机制尚不清楚。因此，本研究试图建立一种在斑马鱼胚胎/幼体中检测补骨脂素诱导发育毒性的方法。补骨脂素处理导致斑马鱼的孵化率和体长降低，畸形率显著升高。补骨脂素处理后还观察到卵黄滞留、心包水肿、鳔缺失和身体弯曲等情况。卵黄滞留可能是由脂质代谢异常引起的。进一步实验表明，补骨脂素对发育中的心脏、肝脏、吞噬细胞和神经系统产生毒性作用。活性氧生成增加、总超氧化物歧化酶活性受到抑制以及丙二醛浓度升高表明抗氧化能力受到抑制且存在氧化应激。与对照组相比，补骨脂素暴露后观察到更多凋亡细胞。此外，基因表达分析结果表明，补骨脂素通过氧化应激、细胞凋亡和能量代谢异常诱导发育毒性。这些发现将有助于理解补骨脂素诱导的毒性。
