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

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.

Keywords:

• N-acetylcysteine (NAC)
• iron oxide nanoparticles
• oxidative stress
• cardiomyocytes
• hypoxia-reoxygenation

Acknowledgments

The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (grant/award numbers: 81500201, 81570223, 81500191, and 81870296) and the Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (grant/award number: PWZxq2017-05).

Disclosure

The authors report no conflicts of interest in this work.