Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
Environ Toxicol Pharmacol. 2022 Jul;93:103885. doi: 10.1016/j.etap.2022.103885. Epub 2022 May 17.
Di (2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer, also known as a developmental toxicant, but its neurobehavioral toxicity remains elusive. This study evaluated the neurobehavioral toxicity and its possible mechanism in larval zebrafish. Embryos at gastrula period (~6 h post fertilization, hpf) were exposure to DEHP (0, 1, 2.5, 5 and 10 mg/L) for 7 days. Spontaneous tail movement in embryos and swimming activity in larvae were monitored. Alterations in the mRNA expression of genes involved in dopamine signaling and apoptosis pathway were assessed. In situ apoptotic cells were assessed by Acridine orange staining, and oxidative damage were measured using enzymatic assay. The behavior results showed that DEHP inhibited spontaneous tail movement and decreased locomotor activities in the light/dark behavioral test. Meanwhile, behavioral changes were accompanied by increased apoptosis and malondialdehyde (MDA) content, decreased superoxide dismutase (SOD) activity and dopamine (DA) content, and perturbed the expression of genes associated with the synthesis (th), reuptake (dat) and metabolism (mao) of DA, with dopamine receptors (DRs), and with the apoptosis pathway (p53, bax, bcl2, caspase-3, caspase-8, caspase-9). The findings will help to illuminate the possible neurobehavioral toxicity mechanisms of organism exposure to DEHP.
邻苯二甲酸二(2-乙基己基)酯(DEHP)是一种广泛使用的增塑剂,也被称为发育毒物,但它的神经行为毒性仍不清楚。本研究评估了邻苯二甲酸二(2-乙基己基)酯(DEHP)在斑马鱼幼鱼中的神经行为毒性及其可能机制。在原肠胚期(约受精后 6 小时,hpf),胚胎暴露于 DEHP(0、1、2.5、5 和 10mg/L)7 天。监测胚胎的自发尾部运动和幼鱼的游泳活动。评估参与多巴胺信号和细胞凋亡途径的基因的 mRNA 表达变化。通过吖啶橙染色评估原位凋亡细胞,并通过酶法测定测量氧化损伤。行为结果表明,DEHP 抑制自发尾部运动并降低明暗行为测试中的运动活性。同时,行为变化伴随着凋亡增加和丙二醛(MDA)含量增加,超氧化物歧化酶(SOD)活性和多巴胺(DA)含量降低,以及与 DA 合成(th)、再摄取(dat)和代谢(mao)相关的基因表达、多巴胺受体(DRs)和细胞凋亡途径(p53、bax、bcl2、caspase-3、caspase-8、caspase-9)失调。这些发现将有助于阐明机体暴露于 DEHP 可能的神经行为毒性机制。