4.4 Article

Ameliorating hydroxychloroquine induced retinal toxicity through cerium oxide nanoparticle treatments

Journal

JOURNAL OF BIOMATERIALS APPLICATIONS
Volume 36, Issue 6, Pages 1033-1041

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/08853282211030150

Keywords

Cerium oxide nanoparticle; hydroxychloroquine; reactive oxygen species; human retinal pigment epithelium; autophagosome; lysosome

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The study investigated the protective effects of cerium oxide nanoparticles (CNP) on human retinal pigment epithelium cells damaged by hydroxychloroquine (HCQ), finding that CNP pre-treatment showed significant protection. This protection mechanism may involve scavenging reactive oxygen species and affecting the colocalization of autophagosomes and lysosomes.
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 mu M 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.

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