2,4-二叔丁基苯酚对斑马鱼早期发育阶段的神经毒性

Neurotoxicity of 2,4-di-tert-butylphenol on the early-staged zebrafish

2,4-二叔丁基苯酚(2,4-di-tert-butylphenol, 2,4-DTBP)作为一种合成酚类抗氧化剂(Synthetic Phenolic Antioxidants, SPAs)被广泛应用于塑料、橡胶、食品等工业产品中,近年来在水体、空气、生物体中被不同程度检出.然而目前有关2,4-DTBP的毒理学研究十分有限,尤其是对鱼类早期发育阶段的神经毒性效应尚未可知.因此,本文以斑马鱼为研究对象,在涵盖环境相关浓度水平上(0.01、0.1和1μmol·L^(-1),即2.06、20.6和206μg·L^(-1)),从运动活性、焦虑行为及多巴胺和5-羟色胺神经信号通路的基因转录水平探讨2,4-DTBP对斑马鱼早期发育阶段的神经毒性效应及其作用机制.结果发现,0.01和0.1μmol·L^(-1) 2,4-DTBP暴露引起仔鱼在暗周期过度活跃,1μmol·L^(-1) 2,4-DTBP暴露引起仔鱼在光周期异常平静及焦虑行为,斑马鱼的行为异常可能与5ht1ab和drd1的过度表达有关.研究表明,2,4-DTBP可能对斑马鱼早期发育阶段具有神经毒性,且不同剂量下的作用机制不同.

2,4-RRdi-RRtert-RRbutylphenol,a typical synthetic phenolic antioxidant,has been widely used in industrial products such as plastics,rubber,and food.In recent years,2,4-DTBP has been detected in water,air,and organisms.However,the neurotoxicity of 2,4-DTBP and the underlying mechanisms were not well documented.In this study,zebrafish embryos were exposed to 0.01,0.1,and 1μmol·L^(-1)(equal 2.06,20.6,and 206μg·L^(-1))2,4-DTBP for 6 days.After exposure,locomotion behavior in dark photokinesis test and light-dark preference test,as well as the expression of genes related to dopamine signaling and serotonin signaling were performed to investigate the toxic effects of 2,4-DTBP in zebrafish larvae.Results showed that 0.01 and 0.1μmol·L^(-1)2,4-DTBP could induce hyperactivity of zebrafish larvae in dark period in dark photokinesis test,which may be related to the over-expression of 5ht1ab and drd1.However,1μmol·L^(-1)2,4-DTBP could cause slightly anxiety-like activity in larvae in light-dark preference test,which might be induced by the up-regulation of drd1.In summary,2,4-DTBP might cause neurotoxicity in early-staged zebrafish,while the toxic mechanism is dose-dependent.