Anti-Inflammatory CeO2 Nanoparticles Prevented Cytotoxicity Due to Exogenous Nitric Oxide Donors via Induction Rather Than Inhibition of Superoxide/Nitric Oxide in HUVE Cells

Molecules

Hisham Alhadlaq¹  Maqusood Ahamed²  Mohd Javed Akhtar² 

[1] Department of Physics and Astronomy, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia;King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia;

关键词: nanoparticles;    ROS;    superoxide;    nitric oxide;    signaling effect;    endothelial cells;   

DOI  :  10.3390/molecules26175416

来源: DOAJ

【 摘 要 】

The mechanism behind the cytoprotective potential of cerium oxide nanoparticles (CeO₂ NPs) against cytotoxic nitric oxide (NO) donors and H₂O₂ is still not clear. Synthesized and characterized CeO₂ NPs significantly ameliorated the lipopolysaccharide (LPS)-induced cytokines IL-1β and TNF-α. The main goal of this study was to determine the capacities of NPs regarding signaling effects that could have occurred due to reactive oxygen species (ROS) and/or NO, since NP-induced ROS/NO did not lead to toxicity in HUVE cells. Concentrations that induced 50% cell death (i.e., IC50s) of two NO donors (DETA-NO; 1250 ± 110 µM and sodium nitroprusside (SNP); 950 ± 89 µM) along with the IC50 of H₂O₂ (120 ± 7 µM) were utilized to evaluate cytoprotective potential and its underlying mechanism. We determined total ROS (as a collective marker of hydrogen peroxide, superoxide radical (O₂^•−), hydroxyl radical, etc.) by DCFH-DA and used a O₂^•− specific probe DHE to decipher prominent ROS. The findings revealed that signaling effects mediated mainly by O₂^•− and/or NO are responsible for the amelioration of toxicity by CeO₂ NPs at 100 µg/mL. The unaltered effect on mitochondrial membrane potential (MMP) due to NP exposure and, again, CeO₂ NPs-mediated recovery in the loss of MMP due to exogenous NO donors and H₂O₂ suggested that NP-mediated O₂^•− production might be extra-mitochondrial. Data on activated glutathione reductase (GR) and unaffected glutathione peroxidase (GPx) activities partially explain the mechanism behind the NP-induced gain in GSH and persistent cytoplasmic ROS. The promoted antioxidant capacity due to non-cytotoxic ROS and/or NO production, rather than inhibition, by CeO₂ NP treatment may allow cells to develop the capacity to tolerate exogenously induced toxicity.

【 授权许可】

Unknown