Abstract：
2-Ethylhexyl diphenyl phosphate (EHDPP) is a frequently utilized organophosphorus flame retardant (OPFR) and has been extensively detected in environmental media. Prolonged daily exposure to EHDPP has been linked to potential retinal damage, yet the adverse impacts on the retina are still generally underexplored. In this research, we explored oxidative stress, inflammation, and the activating mechanisms initiated by EHDPP in mouse retinal photoreceptor (661 W) cells following a 24 h exposure period. Our research demonstrated that EHDPP led to a decline in cell viability that was directly proportional to its concentration, with the median lethal concentration (LC50) being 88 µM. Furthermore, EHDPP was found to elevate intracellular and mitochondrial levels of reactive oxygen species (ROS), trigger apoptosis, induce cell cycle arrest at the G1 phase, and modulate the expression of both antioxidant enzymes (Nrf2, HO-1, and CAT) and pro-inflammatory mediators (TNF-α, IL-1β, and IL-6) within 661 W cells. These findings indicate that retinal damage triggered by EHDPP exposure could be mediated via the Nrf2/HO-1 signaling pathway in these cells. Collectively, our investigation revealed that oxidative stress induced by EHDPP is likely a critical factor in the cytotoxic response of 661 W cells, potentially leading to damage in retinal photoreceptor cells.
摘要：
2-乙基己基二苯基磷酸酯（EHDPP）是一种常用的有机磷阻燃剂（OPFR），已在环境介质中广泛检测到。长期每天接触EHDPP与潜在的视网膜损伤有关，然而，对视网膜的不利影响通常仍未被充分开发。在这项研究中,我们探索了氧化应激，炎症,以及在24小时暴露后，EHDPP在小鼠视网膜光感受器（661W）细胞中引发的激活机制。我们的研究表明，EHDPP导致细胞活力下降，这与它的浓度成正比。中位致死浓度（LC50）为88µM。此外，发现EHDPP可提高活性氧（ROS）的细胞内和线粒体水平，触发细胞凋亡，诱导细胞周期停滞在G1期，并调节抗氧化酶（Nrf2，HO-1和CAT）和促炎介质（TNF-α，IL-1β,和IL-6）在661W细胞内。这些发现表明，EHDPP暴露引发的视网膜损伤可能是通过这些细胞中的Nrf2/HO-1信号通路介导的。总的来说，我们的研究表明，由EHDPP诱导的氧化应激可能是661W细胞的细胞毒性反应的关键因素，可能导致视网膜感光细胞的损伤。
