In vivo assessment of toxicological potential of graphene oxide nanosheets in Sprague Dawley rats
By: Zahid Iqbal, Farhat Jabeen, Tanveer A. Tabish, Tayyaba Sultana, Salma Sultana
Key Words: Graphene oxide nanosheets, in vivo, Sprague Dawley Rats, Oxidative Stress.
Int. J. Biosci. 15(2), 456-474, August 2019.
Certification: ijb 2019 0107 [Generate Certificate]
Graphene oxide nanosheets (GON) have encouraging applications in the field of biology, particularly in drugs delivery and therapeutics due to its distinctive properties. Despite of its greater applications in vivo studies but data of toxicity in vivo is scares. Therefore, a study was designed to assess the in vivo toxic potential of GON in Sprague Dawley rats by involving 25 rats distributed into 5 groups having 5 replicates. The groups were named as control (without any treatment), placebo (receiving deionized water intraperitoneally) and three treated groups (G1-G3) exposed with GON intraperitoneally @ 1.5 or 2.5 or 3.5mg/kg of bodyweight on alternate day for 30 days. After 30 days of exposure toxicity induced by GON was assessed. No death or change in body morphology and behavior were observed during the whole experiment. In present study, exposure of GON @ 2.5 and 3.5mg/kg BW induced toxicity, which was evident by the alteration in somatic index of liver, liver function enzymes concentrations (ALT, AST and ALP), markers of oxidative stress (MDA and LPO), enzymes of antioxidative system (CAT and GSH) and histopathology of liver of treated groups compared with control. Normal histology was observed in control and deionized treated rats while treated rats with GON showed dilation in central vein, pyknotic nuclei and degeneration of hepatocytes in a dose dependent manner. Therefore, much attention is required for the investigation of dose dependent toxicity of GON so that strictly monitored dose could be used in vivo applications.
In vivo assessment of toxicological potential of graphene oxide nanosheets in Sprague Dawley rats
Aebi H. 1974. Catalase. In Methods of enzymatic analysis. Academic press, 673-684.
Akhavan O, Choobtashani M, Ghaderi E. 2012. Protein degradation and RNA efflux of virus’s photocatalyzed by graphene–tungsten oxide composite under visible light irradiation. The Journal of Physical Chemistry 116(17), 9653-9659.
Allen MJ, Tung VC, Kaner RB. 2009. Honeycomb carbon: a review of graphene. Chemical Reviews 110, 132–145.
Almeida JPM, Chen AL, Foster A, Drezek R. 2011. In vivo biodistribution of nanoparticles, Nanomedicine 6(5), 815–835.
Augustine R, Mathew AP, Sosnik A. 2017. Metal oxide nanoparticles as versatile therapeutic agents modulating cell signaling pathways: Linking nanotechnology with molecular medicine. Applied Materials Today 7, 91-103.
Bahadar H, Maqbool F, Niaz K, Abdollahi M. 2016. Toxicity of Nanoparticles and an Overview of Current Experimental Models. Iranian Biomedical Journal 20 (1), 1-11.
Chen GY, Yang HJ, Lu CH, Cho L. 2012. Simultaneous induction of autophagy and toll-like receptor signaling pathways by graphene oxide. Biomaterials 33(27), 6559–6569.
Chen M, Yin J, Liang Y, Yuan S, Wang F, Song M, Wang H. 2016. Oxidative stress and immunotoxicity induced by graphene oxide in zebra fish. Aquatic Toxicology 174, 54–60.
Chowdhury SM, Lalwani G, Zhang K, Yang J Y, Neville K, Sitharaman B. 2013. Cell specific cytotoxicity and uptake of graphene
nanoribbons. Biomaterials 34(1), 283-293.
Chung C, Kim YK, Shin D, Ryoo SR, Hong BH, Min DH. 2013. Biomedical applications of graphene and graphene oxide. Accounts of Chemical Research 46, 2211-24.
Cichoz-Lach H, Michalak A. 2014. Oxidative stress as a crucial factor in liver diseases. World Journal of Gastroenterology 20(25), 8082-8091.
Cohen-Tanugi D, Grosman JC. 2012. Water desalination across nanoporous graphene. Nano letters 12(7), 3602-3608.
Dikin DA, Stankovich S, Zimney EJ, Piner RD, Dommett GH, Evmenenko G, Nguyen ST, Ruoff RS. 2007. Preparation and characterization of graphene oxide paper. Nature 448, 457–460.
Droge W. 2002. Free radicals in the physiological control of cell function. Physiological Reviews 82, 47-95.
Forman HJ, Zhang H, Rinna A. 2009. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine 30(1-2), 1–12.
Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. 2007. The central role of glutathione in the pathophysiology of human diseases. Archives of physiology and biochemistry, 113, 23 258.
Geim AK, Novoselov KS. 2007. The rise of graphene. Nature Materials 6(3), 183–191.
Guo C, Sun L, Cai H, Duan Z, Zhang S, Gong Q, Gu Z. 2017. Gadolinium-labeled biodegradable dendron–hyaluronic acid hybrid and its subsequent application as a safe and efficient magnetic resonance imaging contrast agent. ACS applied materials & interfaces 9(28), 23508-23519.
Habiba K, Bracho-Rincon DP, Gonzalez-Feliciano JA, Villalobos-Santos JC, Makarov VI, Ortiz D, Morell G. 2015. Synergistic antibacterial activity of PEGylated silver–graphene quantum dots nanocomposites. Applied Materials Today, 1(2), 80-87.
Hadi M, Mollaei T. 2019. Reduced graphene oxide/graphene oxide hybrid-modified electrode for electrochemical sensing of tobramycin. Chemical Papers 73(2), 291-299.
Hirsch A. 2010. The era of carbon allotropes. Nature materials 9, 868.
Islam F, Yasmeen T, Ali Q, Ali S, Arif MS, Hussain S, Rizvi H. 2014. Influence of Pseudomonas aeruginosa as PGPR on oxidative stress tolerance in wheat under Zn stress. Ecotoxicology and environmental safety 104, 285-293.
Jiang ZY, Hunt JV, Wolff SD. 1992. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxides in low density lipoprotein. Analytical Biochemistry 202(2), 384-391.
Kale M, Rathore N, John S, Bhatnagar D. 1999. Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocytes: a possible involvement of reactive oxygen species. Toxicology Letters 105(3), 197-205.
Kenry KPL, Lim CT. 2016. Molecular interactions of graphene oxide with human blood plasma proteins. Nanoscale 8(17), 9425-9441.
Khanna P, Ong C, Bay B, Baeg G. 2015. Nanotoxicity: an interplay of oxidative stress, inflammation and cell death. Nanomaterials 5, 1163-80.
Kostarelos K, Novoselov KS. 2014. Exploring the interface of graphene and biology. Science 344(6181), 261-263.
Kostarelos K, Bianco A, Prato M. 2009. Promises, facts and challenges for carbon -nanotubes in imaging and therapeuatics. Nature Nanotechnology 4, 627-33.
Kovbasyuk L, Mokhir A. 2016. Toxicity studies and biomedical applications of graphene oxide. Graphene Oxide: Fundamentals and Applications: John Wiley Sons Ltd. https://onlinelibrary.wiley.com/doi/abs/10.1002/9781119069447
Kumar S, Sharma JG, Maji S, Malhotra BD. 2016. Nanostructured zirconia decorated reduced graphene oxide based efficient biosensing platform for non-invasive oral cancer detection. Biosensors and Bioelectronics 78, 497-504.
Lee DY, Khatun Z, Lee JH, Lee YK, In I. 2011. Blood compatible graphene/heparin conjugate through noncovalent chemistry. Biomacromolecules 12(2), 336-341.
Li B, Zhang X, Yang J, Zhang Y, Li W, Fan C.
- Influence of polyethylene glycol coating on & nbsp; biodistribution and toxicity of nanoscale graphene oxide in mice after intravenous injection. International Journal of Nanomedicine 9, 4697.
Li D, Muller MB, Gilje S. 2008. Processable aqueous dispersions of grapheme nanosheets. Nature Nanotechnology 3, 101-105.
Li N, Zhang Q, Gao S, Song Q, Huang R, Wang L, Cheng G. 2013. Three-dimensional graphene foam as a biocompatible and conductive scaffold for neural stem cells. Scientific reports 3, 1604.
Li Y, Lu Y, Fu Y, Wei T, Le Guyader L, Gao G. 2012. The triggering of apoptosis in macrophages by pristine graphene through MAPK and TGF-beta signaling pathways. Biomaterials 33, 402-11.
Li Y, Wang Y, Tu L, Chen D, Luo Z, Liu D, Miao Z, Feng G, Qing L, Wang S. 2016. Sub-Acute Toxicity Study of Graphene Oxide in the Sprague-Dawley Rat. International Journal of Environmental Research and Public Health 13, 1149.
Lin C, Youbu SU, Takahiro M, Fugetsu B. 2010. Multi-walled carbon nanotubes induce oxidative stress and vacuolar structure changes to Arabidopsis T87 suspension cells. Nano Biomedicine 2(2), 170-181.
Liu J, Cui L, Losic D. 2013. Graphene and graphene oxide as new nanocarriers for drug delivery applications. Acta biomaterialia 9(12), 9243-9257.
Liu Z, Tabakman SM, Chen Z, Dai H. 2009. Preparation of carbon nanotube biocinjugates for biomedical applications. Nature. Protocols 4(9),
Lu SC. 2013. Glutathione synthesis. Biochimica et Biophysica Acta (BBA)-General Subjects 1830(5), 3143-3153.
Manke A, Wang L, Rojanasakul Y. 2013. Mechanisms of nanoparticle induced oxidative stress and toxicity. BioMed Research International 2013.
Mendes RG, Bachmatius A, Buchner B, Cuniberti G, Rummeli MH. 2013. Carbon as nanostructures as multi-functional drug delivery platforms. Journal of Materials Chemistry B 1(4), 401-428.
Merchant CA, Healy K, Wanunu M, Ray V, Peterman N, Bartel J, Drndic M. 2010. DNA translocation through graphene nanopores. Nano letters 10(8), 2915-2921.
Murakami S, Okub K, Tsuji Y, Sakata H, Takahashi T, Kikuchi M. 2004. Changes in liver enzymes after surgery in anti-hepatitis C virus-positive Patients. World Journal of. Surgery 28, 671–674.
Naureen A, Jabeen F, Tabish TA, Yaqub S, Ali M, Chaudhary AS. 2018. Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio. Nanotchnology 29, 1-10.
Nel A, Xia T, Madler L, Li N. 2006. Toxic potential of materials at the nanolevel. Science 311, 622-627.
Nikodinovska VV, Mladenovska K, Grozdanov A. 2015. Risks and health effects from exposure to engineered nanostructures: a critical review. Journal of Chemical Technology and. Metallurgy 50(2), 117-134.
Ohkawa H, Ohishi N, Yagi K. 1979. Analytical Biochemistry 95, 351-8.
Ozdemir OK. 2019. A novel method to produce few layers of graphene as support materials for platinum catalyst. Chemical Papers 73(2), 387-395.
Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. 2008. The current state of serum biomarkers of hepatotoxicity. Toxicology 245(3), 194–205.
Park J, Guo L, Maltzahn G, Ruoslahti E, Bhatia SN, Sailor, MJ. 2009. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Materials 8, 331-336.
Park S, Ruoff RS. 2009. Chemical methods for the production of graphenes. Nature nanotechnology 4(4), 217.
Patlolla AK, Berry A, Tchounwou PB. 2011. Study of hepatotoxicity and oxidative stress in male Swiss-Webster mice exposed to functionalized multi-walled carbon nanotubes. Molecular and Cell Biochemistry 358, 189-199.
Patlolla AK, Randolph J, Kumari SA, Tchounwou PB. 2016. Toxicity Evaluation of Graphene Oxide in Kidneys of Sprague-Dawley Rats. International Journal of Environmental Research and. Public Health 13(4), 380.
Pecoraro R, Angelo D, Filice S, Scalese S, Capparucci F, Marino F, Salvaggio A. 2018. Toxicity evaluation of graphene oxide and titania loaded nafion membranes in zebrafish. Frontiers in physiology 8, 1039.
Priyadarsini S, Sahoo SK, Sahu S, Mukherjee S, Hota G, Mishra M. 2019. Oral administration of graphene oxide nano-sheets induces oxidative stress, genotoxicity, and behavioral teratogenicity in Drosophila melanogaster. Environmental Science and Pollution Research, 1-15.
Qu G, Wang X, Liu Q, Liu R, Yin N, Ma J, Chen L, He J, Liu S, Jiang G. 2013. The ex vivo and in vivo biological performances of graphene oxide and the impact of surfactant on graphene oxide oxide biocompatibility. Journal of Environmental Sciences 25(5), 873-881.
Ramaiah SK. 2007. A toxicologist guide to the diagnostic interpretation of hepaticbiochemical parameters. Food and Chemical Toxicology 45(9), 1551-1557.
Ray DE. 1991. Pesticides derived from plants and other organisms. Handbook of Pesticides Toxicology 2(13), 585-636.
Ribas V, Garcia-Ruiz C, Fernandez-Checa, JC. 2014. Glutathione and mitochondria. Frontiers in pharmacology 5, 151.
Sasidharan A, Panchakarla LS, Sadanandan AR, Ashokan A, Chandran P, Girish CM, Koyakutty M. 2012. Hemocompatibility and macrophage response of pristine and functionalized graphene. Small 8(8), 1251-1263.
Schneider GF, Dekker C. 2012. DNA sequencing with nanopores. Nature biotechnology 30(4), 326.
Schneider GF, Kowalczyk SW, Calado VE, Pandraud G, Zandbergen HW, Vandersypen LM, Dekker C. 2010. DNA translocation through graphene nanopores. Nano letters 10(8), 3163-3167.
Seabra AB, Paula AJ, de Lima R, Alves OL. Duran N. 2014. Nanotoxicity of graphene and graphene oxide. Chemical Research Toxicolology 27, 159-68.
Sedalk J, Lindasy RH. 1968. Analytical Biochemistry 25, 192-205.
Sharma P, Singh R, Jan M. 2014. Dose-dependent effect of deltamethrin in testis, liver, and kidney of Wistar rats. Toxicolology International 21(2), 131-139.
Singh N, Srivastava G, Talat M, Raghubanshi H, Srivastava ON, Kayastha AM. 2014. Cicer α-galactosidase immobilization onto functionalized graphene nanosheets using response surface method and its applications. Food chemistry 142, 430-438.
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(3), 2731-2740.
Surwade SP, Smirnov SN, Vlassiouk IV, Unocic RR, Veith GM, Dai S, Mahurin SM. 2015. Water desalination using nanoporous single-layer graphene. Nature nanotechnology 10(5), 459.
Tabish TA, Zhang S, Winyard PG. 2018. Developing the next generation of graphene-based platforms for cancer therapeutics: The potential role of reactive oxygen species. Redox biology 15, 34-40.
Wan Q, Huang Q, Liu M, Xu D, Huang H, Zhang X, Wei Y. 2017. Aggregation-induced emission active luminescent polymeric nanoparticles: non-covalent fabrication methodologies and biomedical applications. Applied Materials Today 9, 145-160.
Wick P, Louw-Gaume AE, Kucki M, Krug HF, Kostarelos K, Fadeel B, Dawson KA, Salvati A, Vazquez E, Ballerini L, Tretiach M, Benfenati F, Flahaut E, Gauthier L, Prato M, Bianco A. 2014. Classification Framework for Graphene-Based Materials. Angewandte Chemie International Edition 53(30), 7714-7718.
Wu L, Wang J, Yin M, Ren J, Miyoshi D, Sugimoto N, Qu X. 2014. Reduced Graphene Oxide Upconversion Nanoparticle Hybrid for Electrochemiluminescent Sensing of a Prognostic Indicator in Early‐Stage Cancer. Small 10(2), 330-336.
Xu X, Zheng Q, Bai G, Song L, Yao Y, Cao X, Yao C. 2017. Polydopamine induced in-situ growth of Au nanoparticles on reduced graphene oxide as an efficient biosensing platform for ultrasensitive detection of bisphenol A. Electrochimica Acta 242, 56-65.
Yan L, Zhang S, Zeng C, Xue YH, Zhou ZL, Lu F, Liu Y. 2011. Cytotoxicity of single-walled carbon nanotubes with human ocular cells. In Advanced Materials Research 287, 32-36.
Yang D, Velamakanni A, Bozoklu G, Park S, Stoller M, Piner RD, Stankovich S, Jung I, Field DA, Ventrice CA. 2009. Chemical analysis of graphene oxide films after heat and chemical treatments by X-ray photoelectron and Micro-Raman spectroscopy. Carbon 47, 145-152.
Yang K, Gong H, Shi X, Wan J, Zhang Y, Liu Z. 2013. In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration. Biomaterials 34, 2787-95.
Yang K, Li Y, Tan X, Peng R, Liu Z. 2013. Behavior and toxicity of graphene and its functionalized derivatives in biological systems. Small 9(9–10), 1492-503.
Yang K, Wan J, Zhang S, Tian B, Zhang B, Liu Z. 2012. The influence of surface chemistry and particle size of nanoscale graphene oxide on photothermal therapy of cancer using ultra-low laser power. Biomaterials 33, 2206-14.
Yang K, Wan J, Zhang S, Zhang Y, Lee ST, Liu Z. 2011. In vivo pharmacokinetics, long term biodistribution, and toxicology of pegylated graphene in mice. ACS nano 5(1), 516-522.
Zhang J, Chen N, Li M, Feng C. 2017. Synthesis and environmental application of zirconium–chitosan/graphene oxide membrane. Journal of the Taiwan Institute of Chemical Engineers 77, 106-112.
Zhang Y, Wu C, Guo S, Zhang J. 2013. Interactions of graphene and graphene oxide with proteins and peptides. Nanotechnology Reviews 2(1), 27-45.
Zhang Y, Ali SF, Dervishi E, Xu Y, Li Z, Casciano D, Biris AS. 2010. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma derived pc12 cells. ACS Nano 4 (6), 318.
Zhu C, Guo S, Fang Y, Dong S. 2010. Reducing sugar: new functional molecules for the green synthesis of graphene nanosheets. ACS nano 4(4), 2429-2437.
In vivo assessment of toxicological potential of graphene oxide nanosheets in Sprague Dawley rats.
Int. J. Biosci. 15(2), 456-474, August 2019.
By Authors and International Network for
Natural Sciences (INNSPUB)