Oral toxic exposure of titanium dioxide nanoparticles on serum biochemical changes in adult male Wistar rats

Document Type : Research Paper

Authors

1 Department of Zoology, Kanchi Mamunivar Centre for Post Graduate Studies, Puducherry, India

2 Department of Pharmacology, Siddha Central Research Institute, Chennai, India

Abstract

Objective(s):
Titanium dioxide (TiO2) nanoparticles (NPs) are widely used in commercial food additives and cosmetics worldwide. Uptake of these nanoparticulate into humans by different routes and may exhibit potential side effects, lags behind the rapid development of nanotechnology. Thus, the present study designed to evaluate the toxic effect of mixed rutile and anatase TiO2 NPs on serum biochemical changes in rats.

Materials and Methods:
In this study, adult male Wistar rats were randomly allotted into the experimental and control groups (n=6), which were orally administered with 50 and 100 mg/kg body weight of TiO2 NPs. Toxic effects were assessed by the changes of serum biochemical parameters such as glucose, total protein, albumin, globulin, cholesterol, triglyceride, high density lipoprotein, alanine transaminase, aspartate transaminase, alkaline phosphatase, total bilirubin, blood urea nitrogen, uric acid and creatinine. All the serum biochemical markers were experimented in rats, after 14-days of post exposure.
Results:
Changes of the serum specific parameters indicated that liver and kidney were significantly affected in both experimental groups. The changes between the levels of total protein, glucose, aspartate transaminase, alanine transaminase and alkaline phosphatase indicate that TiO2 NPs induces liver damage. Significant increase in the blood urea nitrogen and uric acid indicates the renal damage in the TiO2 NPs treated rats.
Conclusion:
The data shows that the oral administration of TiO2 NPs (<100nm) may lead to hepatic and renal toxicity in experimental rats.

Keywords

References

  1. Robertson TA, Sanchez WY, Roberts MS. Are commercially available nanoparticles safe when applied to the skin? J Biomed Nanotechnol. 2010; 6: 452-468.
  2. Kisin ER, Murray AR, Keane MJ, Shi XC, Schwegler-Berry D, Gorelik O, et al. Single-walled carbon nanotubes: geno-and cytotoxic effects in lung fibroblast V79 cells. J Toxicol Environ Health A. 2007; 70: 2071-2079.
  3. Stark WJ. Nanoparticles in biological systems. Angew Chem Int Ed. 2011; 50: 1242-1258.
  4. Tholouli E, Sweeney E, Barrow E, Clay V, Hoyland JA, Byers RJ. Quantum dots light up pathology. J Pathol. 2008; 216: 275-285.
  5. Brunet L, Lyon DY, Hotze EM, Alvarez PJ, Wiesner MR. Comparative photoactivity and antibacterial properties of C-60 fullerenes and titanium dioxide nanoparticles. Environ Sci Technol. 2009; 43: 4355-4360.
  6. Nemmar A, Melghit K, Ali BH. The acute proinflammatory and prothrombic effects of pulmonary exposure to rutile TiO2 nanorods in rats. Exp Biol Med. 2008; 233: 610-619.
  7. Gelis C, Girard S, Mavon A, Delverdier M, Paillous N, Vicendo P. Assessment of the skin photoprotective capacities of an organo-mineral broad-spectrum sun block on two ex vivo skin models. Photodermatol Photoimmunol Photomed. 2003; 19: 242-253.
  8. Lomer MC, Thompson RP, Powell JJ. Fine and ultrafine particles of the diet: Influence on the mucosal immune response and association with Crohn’s disease. Proc Nutr Soc. 2002; 61: 123-130.
  9. Linkous CA, Carter GJ, Locuson DB. Photocatalytic Inhibition of algae growth using TiO2, WO3 and co-catalyst modifications. Environ Sci Technol. 2000; 34: 4754-4758.
  10. Warheit DB, Hoke RA, Finlay C, Donner EM, Reed KL, Sayes CM. Development of a base of toxicity tests using ultrafine TiO2 particles as a component of nanoparticle risk management. Toxicol Lett. 2007; 171: 99-110.
  11. Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect. 2005; 113(7): 823-839.
  12. Moss OR, Wong VA. When nanoparticles get in the way: impact of projected area on in vivo and in vitro macrophage function. Inhal Toxicol 2006; 18(10): 711-716.
  13. Moller W, Hofer T, Ziesenis A, Karg E, Heyder J. Ultrafine particles cause cytoskeletal dysfunctions in macrophages. Toxicol Appl Pharmcol. 2002; 182(3): 197-207.
  14. Hext PM, Tomenson JA, Thompson P. Titanium dioxide: inhalation toxicology and epidemiology. Ann Occup Hyg. 2005; 49(6): 461-472.
  15. Bermudez E, Mangum JB, Asgharian B, Wong BA, Reverdy EE, Janszen DB, et al. Longterm pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles. Toxicol Sci. 2002; 70: 86-97.     
  16. Donaldson K. Nonneoplastic lung responses induced in experimental animals by exposure to poorly soluble nonfibrous particles. Inhal Toxicol. 2000; 12(1–2): 121-139.
  17. Linhua H, Zhenyu W, Baoshan X. Effect of sub-acute exposure to TiO2 nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio). J Environ Sci. 2009; 21: 1459-1466.
  18. Gurr JR, Wang AS, Chen CH, Jan KY. Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells. Toxicol. 2005; 213: 66-73.
  19. Falck GC, Lindberg HK, Suhonen S, Vippola M, Vanhala E, Catalan J, et al. Genotoxic effects of nanosized and fine TiO2. Human Exp Toxicol. 2009; 28: 339-352.
  20. Wang JX, Fan YB, Gao Y, Hua QH, Wang TC. TiO2 nanoparticles translocation and potential toxicological effect in rats after intra-articular injection. Biomaterials. 2009; 30: 4590-4600.
  21. Vamanu CI, Cimpan MR, Hol PJ, Sornes S, Lie SA, Gjerdet NR. Induction of cell death by TiO2 nanoparticles: Studies on a human monoblastoid cell line. Toxicol In Vitro. 2008; 22: 1689-1696.
  22. Jeng HA, Swanson J. Toxicity of metal oxide nanoparticles in mammalian cells. J Environ Sci Health Part A. 2006; 41: 2699-2711.
  23. Hussain SM, Hess KL, Gearhart JM, Geiss KT, Schlager JJ. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol In Vitro. 2005; 19: 975-983.
  24. FDA. Titanium dioxide. In The United States Code of Federal Regulations, Title 21, Section 73.575, 2005. Office of the Federal Register, Washington, DC.
  25. Shi H, Magaye R, Castranova V, Zhao J. Titanium dioxide nanoparticles: a review of current toxicological data. Part Fibre Toxicol. 2013; 10: 15.
  26. World Health Organization (WHO). FAO Nutrition Meetings Report Series No. 46A: 1969. Toxicological evaluation of some food colours, emulsifiers, stabilizers, anti-caking agents and certain other substances. WHO/ FOOD ADD/70.36.
  27. Bermudez E, Mangum JB, Wong BA, Asgharian B, Hext PM, Warheit DB, et al. Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles. Toxicol Sci. 2004; 77: 347-357.
  28. Grassian VH, O'Shaughnessy PT, Adamcakova-Dodd A, Pettibone JM, Thorne PS. Inhalation exposure study of titanium dioxide nanoparticles with a primary particle size of 2 to 5 nm. Environ Health Perspect. 2007; 115: 397-402.
  29. Wang JX, Li YF, Zhou GQ, Li B, Jiao F, Chen CY, et al. Influence of intranasal instilled titanium dioxide nanoparticles on monoaminergic neurotransmitters of female mice at different exposure time. Zhonghua Yu Fang Yi Xue Za Zhi. 2007; 41(2): 91-95.
  30. Boffetta P, Soutar A, Cherrie JW, Granath F, Anderson A, Anttila A, et al. Mortality among workers employed in the titanium dioxide production industry in Europe. Cancer Causes Control. 2004; 15: 697-706.
  31. Chen JL, Fayerweather WE. Epidemiologic study of workers exposed to titanium dioxide. J Occup Med.  1988; 30(12): 937-942.
  32. International Agency for Research on Cancer (IARC). Carbon black, titanium dioxide, and talc. In IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Lyon, France: World Health Organization, International Agency for Research on Cancer. 2010; 93: 1–452.
  33. Jani PU, Mc-Carthy DE, Florence AT. Titanium dioxide (rutile) particle uptake from the rat GI tract and translocation to systemic organs after oral administration. Int J Pharma. 1994; 105: 157-68.
  34. Fabian E, Landsiedel R, Wiench K, Wohlleben W, Ravenzwaay BV. Tissue distribution and toxicity of intravenously administered titanium dioxide nanoparticles in rats. Arch Toxicol. 2008; 82: 151-157.
  35. Sugibayashi K, Todo H, Kimura E. Safety evaluation of titanium dioxide nanoparticles by their absorption and elimination profiles. J Toxicol Sci. 2008; 33: 293-298.
  36. Wang JX, Zhou GQ, Chen CY, Yu HW, Wang TC, Ma YM. Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration. Toxicol Lett. 2007; 168: 176-185.
  37. Huggins CB, Froehlich JP. High concentration of injected titanium dioxide in abdominal lymph nodes. J Exp Med. 1966; 124: 1099-1106.
  38. Dambach DM, Andrews BA, Moulin F. New technologies and screening strategies for hepatotoxicity: Use of in vitro models. J Toxicol Pathol. 2005; 33: 17-26.
  39. Worth AP, Balls M. Alteration (non-animals) methods for chemical testing: Current status and future prospects. A report prepared by ECVAM and the ECVAM working group on chemicals, Alternative to laboratory animals (ATLA): 2002. P. 71-82.
  40. Popper H. Cholestasis. Annu Rev Med. 1968; 19: 39-56.
  41. Lee JH, Kim YS, Song KS, Ryu HR, Sung JH, Park JD, et al. Biopersistence of silver nanoparticles in tissues from Sprague–Dawley rats. Part Fibre Toxicol. 2013; 10: 36.
  42. Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, et al. Passage of inhaled particles into the blood circulation in humans. Circulation. 2002; 105(4): 411-414.
  43. De-Jong WH, Hagens WI, Krystek P, Burger MC, Sips AJ, Geertsma RE. Particle size-dependent organ distribution
    of gold nanoparticles after intravenous administration. Biomaterials. 2008; 29(12): 1912-1919.
  44. Jain TK, Reddy MK, Morales MA, Leslie-Pelecky DL, Labhasetwar V. Biodistribution, clearance, and biocompatibility of iron oxide magnetic
  45.  
  46. nanoparticles in rats. Mol Pharmacol. 2008; 5(2): 316-327.
  47. Burns AA, Vider J, Ow H, Herz E, Penate-Medina O, Baumgart M, et al. Fluorescent silica nanoparticles with efficient urinary excretion for nanomedicine. Nano Lett. 2009; 9(1): 442-448.
  48. Schipper ML, Iyer G, Koh AL, Cheng Z, Ebenstein Y, Aharoni A, et al. Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. Small. 2009; 5(1): 126-134.
  49. Gao GD, Ze YG, Li B, Zhao XY, Zhang T, Sheng L, et al. Ovarian dysfunction and gene-expressed characteristics of female mice caused by long-term exposure to titanium dioxide nanoparticles. J Hazard Materials. 2012;  243: 19-27.
  50. Liu R, Yin L, Pu Y, Liang G, Zhang J, Su Y, et al. Pulmonary toxicity induced by three forms of titanium dioxide
  51. nanoparticles via intratracheal instillation in rat. Prog Nat Sci. 2009; 573-579.
  52. Meena R, Paulraj R. Oxidative stress mediated cytotoxicity of TiO2 nano anatase in liver and kidney of Wistar rat. Toxicol Environ Chem. 2012; 94(1): 146-16146–163.
Nanomedicine Journal
Volume 2, Issue 1 - Serial Number 1
January 2015
Pages 46-53

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