Gadolinium Oxide Nanoparticles Induce Toxicity in Human Endothelial HUVECs via Lipid Peroxidation, Mitochondrial Dysfunction and Autophagy Modulation

In spite of the potential preclinical advantage of Gd(2)O(3) nanoparticles (designated here as GO NPs) over gadolinium-based compounds in MRI, recent concerns of gadolinium deposits in various tissues undergoing MRI demands a mechanistic investigation. Hence, we chose human to measure umbilical vein endothelial cells (HUVECs) that line the vasculature and relevant biomarkers due to GO NPs exposure in parallel with the NPs of ZnO as a positive control of toxicity. GO NPs, as measured by TEM, had an average length of 54.8 ± 29 nm and a diameter of 13.7 ± 6 nm suggesting a fiber-like appearance. With not as pronounced toxicity associated with a 24-h exposure, GO NPs induced a concentration-dependent cytotoxicity (IC(50) = 304 ± 17 µg/mL) in HUVECs when exposed for 48 h. GO NPs emerged as significant inducer of lipid peroxidation (LPO), reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and autophagic vesicles in comparison to that caused by ZnO NPs at its IC(50) for the same exposure time (48 h). While ZnO NPs clearly appeared to induce apoptosis, GO NPs revealed both apoptotic as well as necrotic potentials in HUVECs. Intriguingly, the exogenous antioxidant NAC (N-acetylcysteine) co-treatment significantly attenuated the oxidative imbalance due to NPs preventing cytotoxicity significantly.