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

Abstract

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 Chen11Department 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 workPurpose: 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

Keywords

• N-acetylcysteine (NAC)
• iron oxide nanoparticles
• Oxidative stress
• Cardiomyocytes
• Hypoxia-Reoxygenation