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

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Abstract

Purpose: 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. Methods and results: Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe3O4 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. Conclusions: NAC modifying could suppress the toxic effects of Fe3O4 nanoparticles in H/ R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.

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Shen, Y., Gong, S., Li, J., Wang, Y., Zhang, X., Zheng, H., … Chen, Y. (2019). Co-loading antioxidant N-acetylcysteine attenuates cytotoxicity of iron oxide nanoparticles in hypoxia/ reoxygenation cardiomyocytes. International Journal of Nanomedicine, 14, 6103–6115. https://doi.org/10.2147/IJN.S209820

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