一种广泛使用的有机磷酸酯阻燃剂(OPFR),磷酸三苯酯(TPP),经常在各种环境媒体和人类中检测到。然而,人类角膜上皮暴露于TPP时对健康风险知之甚少。在这项研究中,人正常角膜上皮细胞(HCECs)用于研究细胞活力,形态学,凋亡,和线粒体膜电位暴露于TPP后,以及它们潜在的分子机制。我们发现TPP以浓度依赖的方式降低细胞活力,具有220μM的半最大抑制浓度(IC50)。此外,TPP显著诱导HCEC细胞凋亡,线粒体膜电位以剂量依赖性方式降低,并改变了凋亡生物标志物基因的mRNA水平(Cytc,Caspase-9,Caspase-3,Bcl-2和Bax)。结果表明,TPP对HCECs的细胞毒性,最终导致细胞凋亡和线粒体膜电位的变化。此外,caspase依赖性线粒体途径可能参与TPP诱导的HCEC细胞凋亡。本研究为TPP的人体角膜毒性研究提供参考,表明OPFR对人类健康的风险不容忽视。
A widely used organophosphate flame retardant (OPFR), triphenyl phosphate (
TPP), is frequently detected in various environmental media and humans. However, there is little known on the human corneal epithelium of health risk when exposed to
TPP. In this study, human normal corneal epithelial cells (HCECs) were used to investigate the cell viability, morphology, apoptosis, and mitochondrial membrane potential after they were exposed to
TPP, as well as their underlying molecular mechanisms. We found that TPP decreased cell viability in a concentration-dependent manner, with a half maximal inhibitory concentration (IC50) of 220 μM. Furthermore,
TPP significantly induced HCEC apoptosis, decreased mitochondrial membrane potential in a dose-dependent manner, and changed the mRNA levels of the apoptosis biomarker genes (Cyt c, Caspase-9, Caspase-3, Bcl-2, and Bax). The results showed that
TPP induced cytotoxicity in HCECs, eventually leading to apoptosis and changes in mitochondrial membrane potential. In addition, the caspase-dependent mitochondrial pathways may be involved in TPP-induced HCEC apoptosis. This study provides a reference for the human corneal toxicity of TPP, indicating that the risks of OPFR to human health cannot be ignored.