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

Authors Shen Y, Gong S, Li J, Wang Y, Zhang X, Zheng H, Zhang Q, You J, Huang Z, Chen Y

Received 24 March 2019

Accepted for publication 26 June 2019

Published 1 August 2019 Volume 2019:14 Pages 6103—6115

DOI https://doi.org/10.2147/IJN.S209820

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Lei Yang


Yunli Shen,1,* Shiyu Gong,1,* Jiming Li,1,* Yunkai Wang,1 Xumin Zhang,1 Hao Zheng,1 Qi Zhang,1 Jieyun You,1 Zheyong Huang,2 Yihan Chen1

1Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, People’s Republic of China; 2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, People’s Republic of China

*These authors contributed equally to this work

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.

Keywords: N-acetylcysteine (NAC), iron oxide nanoparticles, oxidative stress, cardiomyocytes, hypoxia-reoxygenation

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