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通过氧化铈纳米粒子治疗改善羟氯喹引起的视网膜毒性。

Ameliorating hydroxychloroquine induced retinal toxicity through cerium oxide nanoparticle treatments.

机构信息

College of Medicine, University of Central Florida, Orlando, USA.

Advanced Materials Processing and Analysis Center, Nanoscience Technology Center, Department of Materials Science and Engineering, 6243University of Central Florida, Orlando, USA.

出版信息

J Biomater Appl. 2022 Jan;36(6):1033-1041. doi: 10.1177/08853282211030150. Epub 2021 Jul 2.

Abstract

The present study investigated the potential protective effects of cerium oxide nanoparticles (CNP) on human retinal pigment epithelium (ARPE-19) cells damaged by hydroxychloroquine (HCQ). Toxicity of HCQ on the ARPE-19 cells was explored with a dose response trial. CNP rescue both a pre-treatment protocol, where CNP were applied 24 hours prior to HCQ application and a simultaneous treatment protocol where both CNP and HCQ were applied together, were used. In the dose response trial, 250 µM HCQ showed 51.84% cell viability after 24 hours and 32.75% after 48 hours time period. This was selected as model HCQ dose for rescue trials. The simultaneous treatment trials did not show a significant increase in viability compared to model toxic dose. The CNP pre-treatment trials showed a significant increase in cellular viability compared to model toxic dose with 68.03% ± 3.27 viability (p = 4.56E-05) at 24 hours and 51.85% ± 4.96 (p = 1.18E-05) at 48 hours time period. CNP pre-treatment showed significant protection of cells from HCQ induced toxicity. The difference in efficacy of simultaneous and pre-treatment is hypothesized to lie in the cellular localization of CNP. Furthermore, including the reactive oxygen species (ROS) scavenging properties of CNP seems to be responsible for protection, the effect of CNP on autophagosome and lysosome colocalization are also hypothesized to play a significant role.

摘要

本研究探讨了氧化铈纳米粒子(CNP)对羟氯喹(HCQ)损伤的人视网膜色素上皮(ARPE-19)细胞的潜在保护作用。通过剂量反应试验研究了 HCQ 对 ARPE-19 细胞的毒性。使用了 CNP 预处理方案和同时处理方案来挽救细胞。在剂量反应试验中,250µM HCQ 在 24 小时后显示出 51.84%的细胞活力,在 48 小时后显示出 32.75%的细胞活力。这被选为挽救试验的模型 HCQ 剂量。与模型毒性剂量相比,同时处理试验并未显示出细胞活力的显著增加。与模型毒性剂量相比,CNP 预处理试验在 24 小时时显示出显著增加的细胞活力,为 68.03%±3.27(p=4.56E-05),在 48 小时时为 51.85%±4.96(p=1.18E-05)。CNP 预处理显示出对 HCQ 诱导的细胞毒性的显著保护作用。同时处理和预处理的疗效差异据推测在于 CNP 的细胞定位。此外,包括 CNP 的活性氧(ROS)清除特性似乎是保护作用的原因,CNP 对自噬体和溶酶体共定位的影响也被认为起着重要作用。

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