Aluminium oxide nanoparticles (Al2O3-NPs) exposure impairs cardiovascular physiology and elevates health risk – proteomic and molecular mechanistic insights

The interactions of nanoparticles with biomolecules lead to toxicopathological outcomes through various mechanisms including oxidative stress. In this regard, the interplay of oxidative stress with other molecular mechanisms of cytotoxicity during aluminium oxide nanoparticles (Al₂O₃-NPs) induced cardiovascular toxicity was not yet precisely explored. Initially, the human serum protein interaction and its corona composition were explored through the gel/label-free proteomics (nLC-HRMS/MS) method. In addition, endothelial cells (EC) and cardiomyoblasts (CM) cultures were employed along with various oxidative stress and cell stress assays. Further, various expression studies (RT-qPCR, western blot, and immunofluorescence), kinase signalling, and siRNA mediated gene knockout assays were performed. Alongside, the in ovo impact on antioxidant enzymes and metabolomic pathways (¹H NMR) in the heart validated the role of oxidative stress during cardiotoxicity. The current outcome illustrates the dose-dependent increase of cytotoxicity and caspase (3 and 9) activation. The dose-dependent elevation and its synergy with cardiovascular stress signalling (ET-1 and Ang-II) illustrate the prominent role of oxidative stress during toxicity. In conclusion, the current study connects the role of the redox system and molecular stress pathways during Al₂O₃-NPs induced cardiotoxicity which extends the knowledge towards the precise health risk assessment during human exposure.