Abstract
A review of recent literature suggests that bismuth oxide (Bi2O3, referred to as B in this article) nanoparticles (NPs) elicit an appreciable response only after a concentration above 40-50 mu g/mL in different cells all having an epithelial origin, to the best of our knowledge. Here, we report the toxicological profile of Bi2O3 NPs (or BNPs) (71 +/- 20 nm) in a human endothelial cell (HUVE cell line) in which BNPs exerted much steeper cytotoxicity. In contrast to a high concentration of BNPs (40-50 mu g/mL) required to stimulate an appreciable toxicity in epithelial cells, BNPs induced 50% cytotoxicity in HUVE cells at a very low concentration (6.7 mu g/mL) when treated for 24 h. BNPs induced reactive oxygen species (ROS), lipid peroxidation (LPO), and depletion of the intracellular antioxidant glutathione (GSH). BNPs also induced nitric oxide (NO,) which can result in the formation of more harmful species in a fast reaction that occurs with superoxide (O-2(center dot-)). Exogenously applied antioxidants revealed that NAC (intracellular GSH precursor) was more effective than Tiron (a preferential scavenger of mitochondrial O-2(center dot-)) in preventing the toxicity, indicating ROS production is extra-mitochondrial. Mitochondrial membrane potential (MMP) loss mediated by BNPs was significantly less than that of exogenously applied oxidant H2O2, and MMP loss was not as intensely reduced by either of the antioxidants (NAC and Tiron), again suggesting BNP-mediated toxicity in HUVE cells is extra-mitochondrial. When we compared the inhibitory capacities of the two antioxidants on different parameters of this study, ROS, LPO, and GSH were among the strongly inhibited biomarkers, whereas MMP and NO were the least inhibited group. This study warrants further research regarding BNPs, which may have promising potential in cancer therapy, especially via angiogenesis modulation.