Wang Chengqiang, Chen Zihan, Lu Yanmei, Wang Lu, Zhang Yabin, Zhu Xiaonian, Song Jiale
Department of Occupational and Environmental Medicine, School of Public Health, Guilin Medical University, Guilin, Guangxi, China.
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China.
Toxicol Mech Methods. 2020 Sep;30(7):490-496. doi: 10.1080/15376516.2020.1765060. Epub 2020 May 13.
To explore the neurotoxicity and mechanism of tris(2-chloroethyl) phosphate (TCEP) exposure in mice. Total 30 adult Kunming mice were randomly divided into normal control group (0 mg/kg·d), low-dose TCEP group (10 mg/kg·d), and high-dose TCEP group (100 mg/kg·d), and administered continuously by gavage for 30 days. Compared with the control group, the water intake of high-dose TCEP group was declined significantly ( < 0.05), and the organ index of liver and spleen were increased significantly ( < 0.05). In addition, the escape latency of TCEP exposed mice were longer than that in the control group in water maze test ( < 0.05), while the total swimming course of high-dose TCEP group was elevated and the swimming time in target quadrant was obviously shortened compared with the control group ( < 0.05). The serum levels of total-triiodothyronine (TT3) and free triiodothyronine (FT3) were significantly higher in the high-dose TCEP group than in the control group (＜0.05). Compared with the control group, the activities of glutathione transferase (GST) and super oxide dismutase (SOD) in the high-dose TCEP group were increased, and GST in the low-dose TCEP group were decreased, while the content of malonaldehyde (MDA) in both groups was increased (＜0.05). In the CCK8 assay, the viability of PC12 cells decreased with an increase of TCEP concentration, indicating a concentration dependent neurotoxicity. TCEP exposure can cause neurotoxicity by increasing thyroid hormones and inducing oxidative damage in mice.
探讨磷酸三（2-氯乙基）酯（TCEP）染毒小鼠的神经毒性及机制。将30只成年昆明小鼠随机分为正常对照组（0 mg/kg·d）、低剂量TCEP组（10 mg/kg·d）和高剂量TCEP组（100 mg/kg·d），连续灌胃给药30天。与对照组相比，高剂量TCEP组小鼠饮水量显著下降（ < 0.05），肝脏和脾脏脏器指数显著升高（ < 0.05）。此外，在水迷宫实验中，TCEP染毒小鼠的逃避潜伏期长于对照组（ < 0.05），而高剂量TCEP组的总游泳路程增加，与对照组相比，在目标象限的游泳时间明显缩短（ < 0.05）。高剂量TCEP组血清总三碘甲状腺原氨酸（TT3）和游离三碘甲状腺原氨酸（FT3）水平显著高于对照组（＜0.05）。与对照组相比，高剂量TCEP组谷胱甘肽转移酶（GST）和超氧化物歧化酶（SOD）活性升高，低剂量TCEP组GST活性降低，两组丙二醛（MDA）含量均升高（＜0.05）。在CCK8检测中，PC12细胞活力随TCEP浓度增加而降低，表明具有浓度依赖性神经毒性。TCEP染毒可通过增加甲状腺激素和诱导小鼠氧化损伤而导致神经毒性。
