Identification of potential biomarkers of gold nanoparticle toxicity in rat brains

Journal of Neuroinflammation

W Y Ong²  Abdullah S Alhomida³  Afaf K El-Ansary³  Mohamed Anwar K Abdelhalim¹  Nikhat J Siddiqi³ 

[1] Physics & Astronomy, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia;Neurobiology and Ageing Research Program, National University of Singapore, Singapore, 119260, Singapore;Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh, 11495, Saudi Arabia

关键词: Neurotransmitters;    Interferon-γ;    Cell death;    DNA damage;    Antioxidant enzyme;    Oxidative stress;    Gold nanoparticles;   

Others  :  1212536
DOI  :  10.1186/1742-2094-9-123

 received in 2012-03-30, accepted in 2012-05-16,  发布年份 2012

【 摘 要 】

Background

Gold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity.

Methods

Male Wister rats weighing 150–200 g were injected with 20 μg/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma amino-butyric acid and interferon-γ.

Results

In this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-γ in treated animals.

Conclusion

This study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-γ, which may lead to inflammation and DNA damage/cell death.

【 授权许可】

   
2012 Siddiqi et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Sonavane G, Tomada K, Makino K: Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size. Colloids Surf B: Biointerfaces 2008, 66:274-280.
• [2]Zhang XD, Wu HY, Wu D, Wang YY, Chang JH, Zhai ZB, Meng AM, Liu PX, Zhang LA, Fan FY: Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int J Nanomedicine 2010, 5:771-781.
• [3]Aschner M: Nanoparticles: transport across the olfactory epithelium and application to the assessment of brain function in health and disease. Prog Brain Res 2009, 180:141-152.
• [4]Buege JA, Aust SD: Microsomal lipid peroxidation. Methods Enzymol 1978, 105:302-310.
• [5]Wendel A: Glutathione peroxidase. Method Enzymol. 1981, 77:325-333.
• [6]Yang Z, Liu ZW, Allaker RP, Reip P, Oxford J, Ahmad Z, Ren G: A review of nanoparticle functionality and toxicity on the central nervous system. J R Soc Interface 2010, 7:S411-S422. Downloaded from rsif.royalsocietypublishing.org on March 27, 2012
• [7]Oberdo¨rster G, ILSI Research Foundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group: Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy. Part Fibre Toxicol 2005, 2:8. Downloaded from http://www.particleandfibretoxicology.com/content/2/1/8 webcite on 27/3/2012 on March 27, 2012 BioMed Central Full Text
• [8]Brooking J, Davis SS, Illum L: Transport of nanoparticles across the rat nasal mucosa. J Drug Target 2001, 9:267-279.
• [9]Oberdörster G, Elder A, Rinderknecht A: Nanoparticles and the brain: cause for concern? J Nanosci Nanotechnol 2009, 9:4996-5007. Downloaded from http://www.ncbi.nlm.nih.gov/pubmed/19928180 webcite on March 27, 2012
• [10]Li N, Xia T, Nel AE: The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic Biol Med 2008, 44:1689-1699.
• [11]Yan H, Harding JJ: Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J 1997, 328:599-605.
• [12]de Lamirande E, Gagnon C: Human sperm hyperactivation in whole semen and its association with low superoxide scavenging capacity in seminal plasma. Fertil Steril 1993, 59:1291-1295.
• [13]Karihtala P, Soini Y, Vaskivuo L, Bloigu R, Puistola U: DNA adduct 8–hydroxydeoxyguanosine, a novel putative marker of prognostic significance in ovarian carcinoma. Int J Gynecol Cancer 2009, 19:1047-1051.
• [14]Ng CT, Li JJ, Bay BH, Yung LY: Current studies into the genotoxic effects of nanomaterials. J Nucleic Acids 2010, vol. 2010:Article ID 947859. downloaded from http://www.hindawi.com/journals/jna/2010/947859/cta/ webcite on 9/6/2012
• [15]Butterfield DA, Stadtman ER: Protein oxidation processes in aging brain. Adv Cell Aging Gerontol 1997, 2:161-191. Downloaded from http://toxsci.oxfordjournals.org/ webcite by guest on March 23, 2012
• [16]Porter AG, Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999, 6:99-104.
• [17]Zehendner CM, Librizzi L, de Curtis M, Kuhlmann CRW, Luhmann HJ: Caspase-3 contributes to ZO-1 and Cl-5 tight-junction disruption in rapid anoxic neurovascular unit damage. PloS One [electronic resource] 2011, 6:e16760. Downloaded from http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016760 webcite on May 8, 2012
• [18]Kregel KC: Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol 2002, 92:2177-2186. Downloaded from jap.physiology.org on March 23, 2012
• [19]Dawson TM, Dawson VL: Molecular pathways of neurodegeneration in Parkinson’s disease. Science 2003, 302:819-822.
• [20]Deakin JF: Depression and antisocial personality disorder: two contrasting disorders of 5HT function. J Neural Transm Suppl 2003, 64:79-93.
• [21]Daw ND, Kakade S, Dayan P: Opponent interactions between serotonin and dopamine. Neural Netw 2002, 15:603-616.
• [22]Tidey JW, Miczek KA: Social defeat stress selectively alters mesocorticolimbic dopamine release: an in vivo microdialysis study. Brain Res 1996, 721:140-149.
• [23]Abbas SAR: The effects of gold and silver nanoparticles on choline estrase and monoamino oxidase enzymes activities. Int J Chem 2011, 3:61-68.
• [24]Oberdörster G, Oberdörster E, Oberdörster J: Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005, 113:823-839.
• [25]Reale M, Vianale G, Lotti LV, Mariani-Costantini R, Perconti S, Cristaudo A, Leopold K, Antonucci A, Di Giampaolo L, Iavicoli I, Di Gioacchino M, Boscolo P: Effects of palladium nanoparticles on the cytokine release from peripheral blood mononuclear cells of palladium-sensitized women. J Occup Environ Med 2011, 53:1054-1060.