Deferasirox inhibits lipid peroxidation and ferroptosis in human retinal endothelial cells
Objective To observe and preliminarily explore the effects of Deferasirox(DFX)on lipid peroxidation and ferroptosis in human retinal endothelial cells(HREC).Methods A cell experimental study.Divided the in vitro cultured HREC into normal glucose(NG)group,high glucose(HG)group,NG+DFX group,HG+DFX group,NG+DFX+ferric ammonium citrate(FAC)group,and HG+DFX+FAC group.Light microscope was used to observe the morphology of the cells;cell proliferation was detected by Cell Counting Kit-8 assay,and Calcein-AM staining was used to detect the unstable iron pool(LIP)content;enzyme-linked immunosorbent assay reader was used to detect the reactive oxygen species(ROS),malondialdehyde(MDA),glutathione(GSH),and oxidized glutathione(GSSG);Western blot was used to detect the relative protein expression of Glutathione Peroxidase 4(GPX4)and Solute Carrier Family 7 Member 11(SLC7A11).Two-tailed Student t test was used for comparison between the two groups;one-way ANOVA was used for comparison between multiple groups.Results Compared with the HG group and the HG+DFX+FAC group,the cell proliferation rate and the contents of GSH and the relative protein expression of GPX4,and SLC7A11 in the HG+DFX group were significantly increased,and the differences were statistically significant(F=150.70,21.02,26.09,52.62;P＜0.001).The contents of LIP,ROS,MDA,and GSSG were significantly decreased,and the differences were statistically significant(F=807.20,16.94,31.62,19.21;P＜0.001).Conclusions High glucose significantly induces an increase in LIP,lipid peroxidation,and ferroptosis in HREC.Deferasirox inhibits lipid peroxidation and ferroptosis in HREC by downregulating LIP levels.
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