Co-loading antioxidant N-acetylcysteine attenuates cytotoxicity of iron oxide nanoparticles in hypoxia/reoxygenation cardiomyocytes

• Published in: International journal of nanomedicine 2019-08, Vol.14, p.6103-6115
• Main Authors: Shen, Yunli, Gong, Shiyu, Li, Jiming, Wang, Yunkai, Zhang, Xumin, Zheng, Hao, Zhang, Qi, You, Jieyun, Huang, Zheyong, Chen, Yihan
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Acetylcysteine - pharmacology; Adsorption; Animals; Antioxidants; Antioxidants (Nutrients); Antioxidants - pharmacology; Apoptosis - drug effects; Autophagy - drug effects; Biochemistry; Biomedical materials; Cardiomyocytes; Cell Hypoxia - drug effects; Cell Survival - drug effects; Cytotoxicity; Drug dosages; Emulsion polymerization; Endoplasmic Reticulum Stress - drug effects; Enzyme-linked immunosorbent assay; Ferric Compounds - toxicity; Ferric oxide; Heart cells; Hypoxia; Hypoxia-Reoxygenation; Iron compounds; iron oxide nanoparticles; Iron oxides; Magnetite; Magnetite Nanoparticles - toxicity; Magnetite Nanoparticles - ultrastructure; Membrane Potential, Mitochondrial - drug effects; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - pathology; N-acetylcysteine (NAC); Nanoparticles; Newborn infants; Original Research; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Oxygen - pharmacology; Pore size; Porosity; Proteins; Rats; Reactive Oxygen Species - metabolism; Silicon dioxide; Silicon Dioxide - toxicity; Stem cells; Toxicity; Transmission electron microscopy
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S209820

Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs. Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe O nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis. NAC modifying could suppress the toxic effects of Fe O nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.