Co-loading Antioxidant N-acetylcysteine Attenuates Cytotoxicity of Iron Oxide Nanoparticles in Hypoxia/reoxygenation Cardiomyocytes

Overview

Journal Int J Nanomedicine

Publisher Dove Medical Press

Specialty Biotechnology

Date 2019 Aug 27

PMID 31447555

Citations 15

Authors

Yunli Shen

Shiyu Gong

Jiming Li

Yunkai Wang

Xumin Zhang

Hao Zheng

Qi Zhang

Jieyun You

Zheyong Huang

Yihan Chen

Affiliations

Soon will be listed here.

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 FeO 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 FeO nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.

Citing Articles

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References

Gaharwar U, Meena R, Rajamani P . Iron oxide nanoparticles induced cytotoxicity, oxidative stress and DNA damage in lymphocytes. J Appl Toxicol. 2017; 37(10):1232-1244. DOI: 10.1002/jat.3485. View

Hanini A, Schmitt A, Kacem K, Chau F, Ammar S, Gavard J . Evaluation of iron oxide nanoparticle biocompatibility. Int J Nanomedicine. 2011; 6:787-94. PMC: 3090275. DOI: 10.2147/IJN.S17574. View

Shen Y, Huang Z, Liu X, Qian J, Xu J, Yang X . Iron-induced myocardial injury: an alarming side effect of superparamagnetic iron oxide nanoparticles. J Cell Mol Med. 2015; 19(8):2032-5. PMC: 4549053. DOI: 10.1111/jcmm.12582. View

Srinivas A, Rao P, Selvam G, Goparaju A, Murthy P, Reddy P . Oxidative stress and inflammatory responses of rat following acute inhalation exposure to iron oxide nanoparticles. Hum Exp Toxicol. 2012; 31(11):1113-31. DOI: 10.1177/0960327112446515. View

Wang C, Jia H, Zhu L, Zhang H, Wang Y . Toxicity of α-FeO nanoparticles to Artemia salina cysts and three stages of larvae. Sci Total Environ. 2017; 598:847-855. DOI: 10.1016/j.scitotenv.2017.04.183. View

Gordan R, Wongjaikam S, Gwathmey J, Chattipakorn N, Chattipakorn S, Xie L . Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update. Heart Fail Rev. 2018; 23(5):801-816. PMC: 6093778. DOI: 10.1007/s10741-018-9700-5. View

Lou L, Geng B, Chen Y, Yu F, Zhao J, Tang C . Endoplasmic reticulum stress involved in heart and liver injury in iron-loaded rats. Clin Exp Pharmacol Physiol. 2009; 36(7):612-8. DOI: 10.1111/j.1440-1681.2008.05114.x. View

Sadeghnia H, Zoljalali N, Hanafi-Bojd M, Nikoofal-Sahlabadi S, Malaekeh-Nikouei B . Effect of mesoporous silica nanoparticles on cell viability and markers of oxidative stress. Toxicol Mech Methods. 2015; 25(6):433-9. View

Wang W, Mao Q, He H, Zhou M . Fe3O4 nanoparticles as an efficient heterogeneous Fenton catalyst for phenol removal at relatively wide pH values. Water Sci Technol. 2013; 68(11):2367-73. DOI: 10.2166/wst.2013.497. View

10.

Hua Z, Ma W, Bai X, Feng R, Yu L, Zhang X . Heterogeneous Fenton degradation of bisphenol A catalyzed by efficient adsorptive Fe3O4/GO nanocomposites. Environ Sci Pollut Res Int. 2014; 21(12):7737-45. DOI: 10.1007/s11356-014-2728-8. View

11.

Luo C, Li Y, Yang L, Wang X, Long J, Liu J . Superparamagnetic iron oxide nanoparticles exacerbate the risks of reactive oxygen species-mediated external stresses. Arch Toxicol. 2014; 89(3):357-69. DOI: 10.1007/s00204-014-1267-x. View

12.

Sadeghi L, Tanwir F, Yousefi Babadi V . Antioxidant effects of alfalfa can improve iron oxide nanoparticle damage: Invivo and invitro studies. Regul Toxicol Pharmacol. 2016; 81:39-46. DOI: 10.1016/j.yrtph.2016.07.010. View

13.

Manickam V, Periyasamy M, Dhakshinamoorthy V, Panneerselvam L, Perumal E . Recurrent exposure to ferric oxide nanoparticles alters myocardial oxidative stress, apoptosis and necrotic markers in male mice. Chem Biol Interact. 2017; 278:54-64. DOI: 10.1016/j.cbi.2017.10.003. View

14.

Hayyan M, Hashim M, AlNashef I . Superoxide Ion: Generation and Chemical Implications. Chem Rev. 2016; 116(5):3029-85. DOI: 10.1021/acs.chemrev.5b00407. View

15.

Chen J, Rogers S, Kavdia M . Analysis of kinetics of dihydroethidium fluorescence with superoxide using xanthine oxidase and hypoxanthine assay. Ann Biomed Eng. 2012; 41(2):327-37. PMC: 3544990. DOI: 10.1007/s10439-012-0653-x. View

16.

Singh N, Jenkins G, Nelson B, Marquis B, Maffeis T, Brown A . The role of iron redox state in the genotoxicity of ultrafine superparamagnetic iron oxide nanoparticles. Biomaterials. 2011; 33(1):163-70. DOI: 10.1016/j.biomaterials.2011.09.087. View

17.

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

18.

Wongjaikam S, Kumfu S, Khamseekaew J, Sripetchwandee J, Srichairatanakool S, Fucharoen S . Combined Iron Chelator and Antioxidant Exerted Greater Efficacy on Cardioprotection Than Monotherapy in Iron-Overloaded Rats. PLoS One. 2016; 11(7):e0159414. PMC: 4948821. DOI: 10.1371/journal.pone.0159414. View

19.

Naqvi S, Samim M, Abdin M, Jalees Ahmed F, Maitra A, Prashant C . Concentration-dependent toxicity of iron oxide nanoparticles mediated by increased oxidative stress. Int J Nanomedicine. 2010; 5:983-9. PMC: 3010160. DOI: 10.2147/IJN.S13244. View

20.

Wu X, Tan Y, Mao H, Zhang M . Toxic effects of iron oxide nanoparticles on human umbilical vein endothelial cells. Int J Nanomedicine. 2010; 5:385-99. PMC: 2950396. DOI: 10.2147/ijn.s10458. View