Superparamagnetic iron oxide nanoparticles (SPIONs) have great potential for use in medicine, but they may cause side effects due to oxidative stress. In our study, we investigated the effects of SPIONs on endothelial cells and whether oleic acid (OA) can protect the cells from their harmful effects. We used viability assays, flow cytometry, protein immunodetection, infrared spectroscopy, fluorescence microscopy, and transmission electron microscopy. Our results show that SPIONs are internalized by HUVEC cells, where they induce oxidative stress and lipid peroxidation and cause cell death. Exposure to SPIONs induced accumulation of lipid droplets (LD) that was not dependent on diacylglycerol acyltransferase (DGAT)-mediated LD biogenesis, suggesting that SPIONs suppress LD degradation. Addition of exogenous OA promoted LD biogenesis and reduced SPION-dependent increases in oxidative stress, lipid peroxidation, and cell death. However, exogenous OA protected cells from SPION-induced cell damage even in the presence of DGAT inhibitors, suggesting that LDs are not required for the protective effect of exogenous OA. The molecular phenotype of cells determined by Fourier transform infrared spectroscopy confirmed the destructive effect of SPIONs and the ameliorative role of OA in the case of oxidative stress. Thus, exogenous OA protects endothelial cells from SPION-induced oxidative stress, lipid peroxidation, and cell death independent of its incorporation into triglycerides.
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