Abstract
Nanomaterials have been widely used in a number of applications; however, these nanomaterials may potentially be risky for human health, particularly for the respiratory system. In this study, we used a mouse asthma model to study whether graphene oxide (GO), a promising carbonaceous nanomaterial with unique physicochemical properties, aggravates allergic asthma via the oxidative stress pathway. Mice were sensitized with ovalbumin (OVA) to trigger immune reactions, while vitamin E (Ve) was administered as an antioxidant. Our results showed that GO aggravated OVA-induced allergic asthma in mice, as suggested by increased reactive oxygen species (ROS), elevated total immunoglobulin E (IgE), upregulated Th2 response, and the aggravation of allergic asthma symptoms, such as airway remolding, collagen deposition with mucus hypersecretion, and airway hyperresponsiveness (AHR). The administration of Ve dramatically attenuated all of the above effects. In conclusion, Ve showed anti-allergic properties in antagonizing the exacerbation of allergic asthma induced by GO, providing a new possibility for the treatment of allergic asthma.
Similar content being viewed by others
References
Busse WW, Lemanske RF Jr (2001) Asthma. N Engl J Med 344:350–362
Chen HQ, Gao D, Wang B, Zhao RF, Guan M, Zheng LN, Zhou XY, Chai ZF, Feng WY (2014) Graphene oxide as an anaerobic membrane scaffold for the enhancement of B. adolescentis proliferation and antagonistic effects against pathogens E. coli and S. aureus. Nanotechnology 25:165101
Ding Z, Zhang Z, Ma H, Chen Y (2014) In vitro hemocompatibility and toxic mechanism of graphene oxide on human peripheral blood T lymphocytes and serum albumin. ACS Appl Mater Interfaces 6:19797–19807
Duch MC, Budinger GR, Liang YT, Soberanes S, Urich D, Chiarella SE, Campochiaro LA, Gonzalez A, Chandel NS, Hersam MC, Mutlu GM (2011) Minimizing oxidation and stable nanoscale dispersion improves the biocompatibility of graphene in the lung. Nano Lett 11:5201–5207
Dworski R, Han W, Blackwell TS, Hoskins A, Freeman ML (2011) Vitamin E prevents NRF2 suppression by allergens in asthmatic alveolar macrophages in vivo. Free Radic Biol Med 51:516–521
Edwards MR, Bartlett NW, Clarke D, Birrell M, Belvisi M, Johnston SL (2009) Targeting the NF-kappa B pathway in asthma and chronic obstructive pulmonary disease. Pharmacol Ther 121:1–13
Gorowiec MR, Borthwick LA, Parker SM, Kirby JA, Saretzki GC, Fisher AJ (2012) Free radical generation induces epithelial-to-mesenchymal transition in lung epithelium via a TGF-beta1-dependent mechanism. Free Radic Biol Med 52:1024–1032
Guo J, Han B, Qin L, Li B, You H, Yang J, Liu D, Wei C, Nanberg E, Bornehag CG, Yang X (2012) Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl) phthalate in ovalbumin-immunized BALB/c mice. PLoS One 7:e39008
Gurunathan S, Han JW, Dayem AA, Eppakayala V, Kim JH (2012) Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa. Int J Nanomedicine 7:5901–5914
Gurunathan S, Han JW, Eppakayala V, Kim JH (2013) Green synthesis of graphene and its cytotoxic effects in human breast cancer cells. Int J Nanomedicine 8:1015–1027
Gustafsson A, Jonasson S, Sandstrom T, Lorentzen JC, Bucht A (2014) Genetic variation influences immune responses in sensitive rats following exposure to TiO2 nanoparticles. Toxicology 326:74–85
Han B, Guo J, Abrahaley T, Qin L, Wang L, Zheng Y, Li B, Liu D, Yao H, Yang J, Li C, Xi Z, Yang X (2011) Adverse effect of nano-silicon dioxide on lung function of rats with or without ovalbumin immunization. PLoS One 6:e17236
Hollingsworth JW (2015) Retraction: hyaluronan activation of the Nlrp3 inflammasome contributes to the development of airway hyperresponsiveness. Environ Health Perspect 123:A172
Inoue K, Yanagisawa R, Koike E, Nishikawa M, Takano H (2010) Repeated pulmonary exposure to single-walled carbon nanotubes exacerbates allergic inflammation of the airway: possible role of oxidative stress. Free Radic Biol Med 48:924–934
Jang S, Hwang E, Lee JH, Park HS, Cho JH (2015) Graphene-graphene oxide floating gate transistor memory. Small 11:311–318
Jonasson S, Gustafsson A, Koch B, Bucht A (2013) Inhalation exposure of nano-scaled titanium dioxide (TiO2) particles alters the inflammatory responses in asthmatic mice. Inhal Toxicol 25:179–191
Kang GS, Gillespie PA, Gunnison A, Moreira AL, Tchou-Wong KM, Chen LC (2011) Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model. Environ Health Perspect 119:176–181
Kannan AK, Sahu N, Mohanan S, Mohinta S, August A (2013) IL-2-inducible T-cell kinase modulates T(H)2-mediated allergic airway inflammation by suppressing IFN-gamma in naive CD4(+) T cells. J Allergy Clin Immunol 132:811-+
Lammel T, Boisseaux P, Fernandez-Cruz ML, Navas JM (2013) Internalization and cytotoxicity of graphene oxide and carboxyl graphene nanoplatelets in the human hepatocellular carcinoma cell line Hep G2. Particle Fibre Toxicol 10:27
Lezmi G, Gosset P, Deschildre A, Abou-Taam R, Mahut B, Beydon N, de Blic J (2015) Airway remodeling in preschool children with severe recurrent wheeze. Am J Respir Crit Care Med 192(2):164–171
Li J, Li L, Chen H, Chang Q, Liu X, Wu Y, Wei C, Li R, Kwan JK, Yeung KL, Xi Z, Lu Z, Yang X (2014) Application of vitamin E to antagonize SWCNTs-induced exacerbation of allergic asthma. Sci Rep 4:4275
Ma P, Wu Y, Zeng Q, Gan Y, Chen J, Ye X, Yang X (2013) Oxidative damage induced by chlorpyrifos in the hepatic and renal tissue of Kunming mice and the antioxidant role of vitamin E. Food Chem Toxicol 58:177–183
Madl AK, Plummer LE, Carosino C, Pinkerton KE (2014) Nanoparticles, lung injury, and the role of oxidant stress. Annu Rev Physiol 76:447–465
Park HJ, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, Chun SH, Kim MJ, Choi IW, Ahn SC, Shin YK, Yeom SR, Park YM (2009) Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol 9:261–267
Peters EA, Hiltermann JT, Stolk J (2001) Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med 31:1442–1447
Qian Y, Qiu M, Wu Q, Tian Y, Zhang Y, Gu N, Li S, Xu L, Yin R (2014) Enhanced cytotoxic activity of cetuximab in EGFR-positive lung cancer by conjugating with gold nanoparticles. Sci Rep 4:7490
Qu G, Liu S, Zhang S, Wang L, Wang X, Sun B, Yin N, Gao X, Xia T, Chen JJ, Jiang GB (2013) Graphene oxide induces toll-like receptor 4 (TLR4)-dependent necrosis in macrophages. ACS Nano 7:5732–5745
Romagnani S (2004) Immunologic influences on allergy and the TH1/TH2 balance. J Allergy Clin Immunol 113:395–400
Shurin MR, Yanamala N, Kisin ER, Tkach AV, Shurin GV, Murray AR, Leonard HD, Reynolds JS, Gutkin DW, Star A, Fadeel B, Savolainen K, Kagan VE, Shvedova AA (2014) Graphene oxide attenuates Th2-type immune responses, but augments airway remodeling and hyperresponsiveness in a murine model of asthma. ACS Nano 8:5585–5599
Singh SK, Singh MK, Kulkarni PP, Sonkar VK, Gracio JJ, Dash D (2012) Amine-modified graphene: thrombo-protective safer alternative to graphene oxide for biomedical applications. ACS Nano 6:2731–2740
Sisler JD, Pirela SV, Friend S, Farcas M, Schwegler-Berry D, Shvedova A, Castranova V, Demokritou P, Qian Y (2014) Small airway epithelial cells exposure to printer-emitted engineered nanoparticles induces cellular effects on human microvascular endothelial cells in an alveolar-capillary co-culture model. Nanotoxicology 9(6):769–779
Wang J, Sun P, Bao Y, Dou B, Song D, Li Y (2012) Vitamin E renders protection to PC12 cells against oxidative damage and apoptosis induced by single-walled carbon nanotubes. Toxicol vitro: Int J Published Assoc BIBRA 26:32–41
Zhang H, Liu H, Davies KJ, Sioutas C, Finch CE, Morgan TE, Forman HJ (2012) Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med 52:2038–2046
Acknowledgments
This work was funded by National Natural Science Foundation of China (81372948 and 21577045), Research Fund for the Doctoral Program of Higher Education (20130182120025), and Chongqing Natural Science Foundation (cstc2012jjA1137).
Author’s contributions
Shuai Shang, Jinquan Li, Zhuge Xi, Xu Yang, and Rui Li conceived and designed the experiments. Shuai Shang, Jinquan Li, and Yun Zhao performed the experiments. Shuai Shang, Jinquan Li, Zhisong Lu, Xu Yang, and Rui Li analyzed the data. Zhuge Xi, Zhisong Lu, Xu Yang, and Baizhan Li contributed reagents, materials, and analysis tools. Shuai Shang, Jinquan Li, Zhisong Lu, Xu Yang, and Rui Li wrote the manuscript. All authors have given approval to the final version of the manuscript.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Compliance with National Institutes of Health Guide for the Care and Use of Laboratory Animals, and were approved by the Office of Scientific Research Management of Central China Normal University (No. CCNU-SKY-201-008).
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Responsible Editor: Philippe Garrigues
Shuai Shang and Jinquan Li contributed equally to this work.
Rights and permissions
About this article
Cite this article
Shang, S., Li, J., Zhao, Y. et al. Oxidized graphene-aggravated allergic asthma is antagonized by antioxidant vitamin E in Balb/c mice. Environ Sci Pollut Res 24, 1784–1793 (2017). https://doi.org/10.1007/s11356-016-7903-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-016-7903-7