Naringenin protects RPE cells from NaIO3-induced oxidative damage in vivo and in vitro through up-regulation of SIRT1

Published:1 January 2021 DOI: 10.1016/j.phymed.2020.153375 PMID: 33096452

Wenpei Chen , Bingqing Lin , Shichuan Xie , Wei Yang , Junli Lin , Zhaojia Li , Yaxian Zhan , Shuhua Gui , Baoqin Lin

Abstract

Background

Dry age-related macular degeneration (dAMD) leads to serious burden of visual impairment and there is no definitive treatment. Previous studies have showed that naringenin (NAR) significantly increased electroretinography (ERG) c-wave in sodium iodate (NaIO₃)-treated rats and viability of NaIO₃-treated ARPE-19 cells. But the underlying mechanism is still unknown.

Purpose

We tested the hypothesis that anti-oxidation mediated by Sirtuin 1 (SIRT1) was important to the protective effect of NAR on dAMD.

Study design/Methods

NaIO₃-induced mice retinopathy and ARPE-19 cells injury models were established. In vivo, the protective effect of NAR eye drops on retina was evaluated by flash ERG (FERG) recording and histopathological examination. In vitro, viability of ARPE-19 cells, and the levels of lactic dehydrogenase (LDH), reactive oxygen species (ROS) and carbonyl protein were detected. Protein expression of SIRT1 was analyzed by immunochemical staining, immunofluorescence and western blotting.

Results

NAR eye drops improved retinal function and morphology and normalized the protein expression of SIRT1 in mice exposed to NaIO₃. NAR promoted the survival of ARPE-19 cells in a concentration-dependent manner. NAR up-regulated SIRT1 protein expression, and decreased levels of ROS and carbonyl protein. Moreover, EX527, a selective inhibitor of SIRT1, abolished the effects of NAR on the cell viability and ROS. In addition, SRT1720, a selective agonist of SIRT1, improved the viability of cells and suppressed the production of ROS.

Conclusion

Our findings indicate that SIRT1-mediated anti-oxidation contributes to the protective effect of NAR eye drops on dAMD.