The effect of titanium dioxide nanoparticles on mice midbrain substantia nigra

Document Type : Original Article

Authors

1 Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Microanatomy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Widely used Titanium dioxide nanoparticles (TiO2) enter into the body and cause various organ damages. Therefore, we aimed to study the effect of TiO2 on the substantia nigra of midbrain.
Materials and Methods: 40 male BALB/c mice were randomly divided into five groups: three groups received TiO2 at doses of 10, 25, and 50 mg/kg, the fourth group received normal saline for 45 days by gavage, and control group (without intervention). Then, Motor tests including pole and hanging tests were done to investigate motor disorders. The animal brain was removed for histological purposes. Accordingly, immunohistochemistry was performed to detect tyrosine hydroxylase positive cells, and then toluidine blue staining was done to identify dark neurons in the substantia nigra. Eventually, the total number of these neurons were counted using stereological methods in different groups.
Results: The results showed that the time recorded for mice to turn completely downward on the pole in the TiO2-50 group increased and also the time recorded for animals to hang on the wire in the hanging test significantly decreased (P<0.05) in comparison with other groups. Also, the average number of tyrosine hydroxylase positive neurons in TiO2-25 and TiO2-50 groups significantly decreased as compared to the TiO2-10 and control groups (P<0.05). The total number of dark neurons in the TiO2-25 and TiO2-50 groups was substantially higher than the TiO2-10, control and normal saline groups (P<0.05).
Conclusion: Our findings indicated that TiO2, depending on dose, can cause the destruction of dopaminergic neurons and consequently increase the risk of Parkinson’s disease.

Keywords

Main Subjects

References

1. Chen X, Mao S. Titanium dioxide nanomaterials: synthesis, properties, modifications, and applications. Chem Rev 2007; 107:2891-2959.
2. Lan Y, Lu Y, Ren Z. Mini review on photocatalysis of titanium dioxide nanoparticles and their solar applications. Nano Energy 2013; 2:1031-1045.
3. Lusvardi G, Barani C, Giubertoni F, Paganelli G. Synthesis and characterization of TiO2 nanoparticles for the reduction of water pollutants. Materials 2017; 10:1208-1214.
4. Liu S, Xu L, Zhang T, Ren G, Yang Z. Oxidative stress and apoptosis induced by nanosized titanium dioxide in PC12 cells. Toxicology 2010; 267:172-177.
5. Song B, Liu J, Feng X, Wei L, Shao L. A review on potential neurotoxicity of titanium dioxide nanoparticles. Nanoscale Res Lett 2015; 10:342-354.
6. Shin JA, Lee EJ, Seo SM, Kim HS, Kang JL, Park EM. Nanosized titanium dioxide enhanced inflammatory responses in the septic brain of mouse. Neuroscience 2010; 165:445-454.
7. Gheshlaghi ZN, Riazi GH, Ahmadian S, Ghafari M, Mahinpour R. Toxicity and interaction of titanium dioxide nanoparticles with microtubule protein. Acta Biochim Biophys Sin 2008; 40:777-782.
8. Wang J, Chen C, Liu Y, Jiao F, Li W, Lao F, et al. Potential neurological lesion after nasal instillation of TiO2 nanoparticles in the anatase and rutile crystal phases. Toxicol Lett 2008; 183:72-80.
9. Disdier C, Chalansonnet M, Gagnaire F, Gate L, Cosnier F, Devoy J, et al. Brain inflammation, blood brain barrier dysfunction and neuronal synaptophysin decrease after inhalation exposure to titanium dioxide nano-aerosol in aging rats. Sci Rep 2017; 7:12196-12208.
10. Liu H, Ma L, Zhao J, Liu J, Yan J, Ruan J, et al. Biochemical toxicity of nano-anatase TiO2 particles in mice. Biol Trace Elem Res 2009; 129:170-180.
11. Mohammadipour A, Fazel A, Haghir H, Motejaded F, Rafatpanah H, Zabihi H, et al. Maternal exposure to titanium dioxide nanoparticles during pregnancy; impaired memory and decreased hippocampal cell proliferation in rat offspring. Environ Toxicol Pharmacol 2014; 37:617-625.
12. Mohammadipour A, Hosseini M, Fazel A. The effects of exposure to titanium dioxide nanoparticles during lactation period on learning and memory of rat offspring. Toxicol Ind Health 2016; 32: 221-228.
13. Shimizu M, Tainaka H, Oba T, Mizuo K, Umezawa M, Takeda K. Maternal exposure to nanoparticle titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse. Part Fibre toxicol 2009; 6:20-29.
14. Huerta-Garcia E, Pere-Arizti J, Marquez-Ramirez S, Delgado-Buenrostro N, Chirino Y, Iglesias G, et al. Titanium dioxide nanoparticles induce strong oxidative stress and mitochondrial damage in glial cells. Free Radic Biol Med 2014; 73:84-94.
15. Long TC, Tajuba J, Sama P, Saleh N, Swartz C, Parker J, et al. Nanosize titanium dioxide stimulates reactive oxygen species in brain microglia and damages neurons. Environ Health Perspect 2007; 115:1631-1637.
16. Song B, Zhang Y, Liu J, Feng X, Zhou T, Shao L. Unraveling the neurotoxicity of titanium dioxide nanoparticles: focusing on molecular mechanisms. Beilstein J Nanotechnol 2016; 7:645-54.
17.  Hu R, Gong X, Duan Y, Li N, Che Y, Cui Y, et al. Neurotoxicological effects and the impairment of spatial recognition memory in mice caused by exposure to TiO2 nanoparticles. Biomaterials 2010; 31:8043-8050.
18. Lotfipour AK, Wharton S, Schwarz ST. High resolution magnetic susceptibility mapping of the substantia nigra in Parkinson’s disease. J Magn Reson Imaging 2012; 35:48-55.
19. Chung V, Liu L, Bian Z, Zhao Z, Fong W, Fung-Kum W, et al. Efficacy and safety of herbal medicines for idiopathic Parkinson’s disease: a systematic review. Mov Disord 2006; 21:1709-1715.
20. Taylor TN, Greene JG, Miller GW. Behavioral phenotyping of mouse models of Parkinson’s disease. Behav Brain Res 2010; 211:1-10.
21. Li X, Yu J, Li J, Wu Y, Li B. Dopaminergic dysfunction in mammalian dopamine neurons induced by simazine neurotoxicity. Int J Mol Sci 2017; 18:2404-2412.
22. Ze Y, Sheng L, Zhao X, Hong J, Ze X, Yu X, et al. Tio2 nanoparticles induce hippocampal neuroinflamation in mice. PlOS One 2014; 9:92230-92240.
23. Ahn S, Song TJ, Park SU, Jeon S, Kim J, Oh J, et al. Effects of a combination treatment of KD5040 and L-dopa in a mouse model of Parkinson’s disease. BMC Complement Altern Med 2017; 17:220-232.
24. Jalayeri-Darbandi Z, Rajabzadeh A, Hosseini M, Beheshti F, Ebrahimzadeh-bideskan AR. The effect of methamphetamine exposure during pregnancy and lactation on hippocampal doublecortin expression, learning and memory of rat offspring. Anat Sci Int 2018; 93: 351-363.
25. Mohammadzadeh E, Nikravesh MR, Jalali M, Fazel A, Ebrahimi V, Ebrahimzadeh-bideskan A. Immunohistochemical study of type III collagen expression during pre and post-natal rat skin morphogenesis. Iran J Basic Med Sci 2014; 17:196-200.
26. Baghishani F, Mohammadipour A, Hosseinzadeh H, Hosseini M, Ebrahimzadeh-bideskan A. The effects of tramadol administration on hippocampal cell apoptosis, learning and memory in adult rats and neuroprotective effects of crocin. Metab Brain Dis 2018; 33:907-916.
27. Bagheri-abassi F, Alavi H, Mohammadipour A, Motejaded F, Ebrahimzadeh-bideskan A. The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus. Iran J Basic Med Sci 2015; 18:644-648.
28. Pourzaki M, Homayoun M, Sadeghi S, Seghatoleslam M, Hosseini M, Ebrahimzadeh-bideskan A. Preventive effect of coriandrum sativum on neuronal damages in pentylentetrazole-induced seizure in rats. Avicenna J Phytomed 2017; 7:116-128.
29. Hu Q, Guo F, Zhao F, Fuet Z. Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. Chemosphere 2017; 173:373-379.
30. Disdier C, Devoy J, Cosnefroy A, Chalansonnet M, Herlin-Boime N, Brun E, et al. Tissue bio distribution of intravenously administrated titanium dioxide nanoparticles revealed blood-brain barrier clearance and brain inflammation in rat. Part Fibre Toxicol 2015; 12:27-36.
31. Huot P, Parent A. Dopaminergic neurons intrinsic to the striatum. J Neurochem 2007; 101:1441-1447.
32. Chinta SJ, Andersen JK. Dopaminergic neurons. Int J Biochem Cell Biol 2005; 37:942-946.
33. Carlsson A. The occurrence, distribution and physiological role of catecholamine in the nervous system. Pharmacol Rev 1959; 11:490-493.
34. Anden NE, Carlsson A, Dahlstrom A, Fuxe K, Hillrp NA, Larsson K. Demonstration and mapping out of nigro-neostriatal dopamine neurons. Life Sci 1964; 3:523-530.
35. Bido S, Marti M, Morari M. Amantadine attenuates levodopa‐induced dyskinesia in mice and rats preventing the accompanying rise in nigral GABA levels. J Neurochem 2011; 118:1043-1055.
36. Zhang X, Yin H, Li Z, Zhang T, Yang Z. Nano-TiO2 induces autophagy to protect against cell death through antioxidative mechanism in podocytes. Cell Biol Toxicol 2016; 32:513-527.
37. Khadrawy YA, Salem AM, El-Shamy KA, Ahmed E, Fadi N, Hosny E. Neuroprotective and therapeutic effect of caffeine on the rat model of Parkinson’s disease induced by rotenone. J Diet Suppl 2017; 14:553-572.
38. Grissa I, Guezguez S, Ezzi L, Chakroun S, Sallem A, Kerkeni E, et al. The effect of titanium dioxide nanoparticles on neuroinflammation response in rat brain. Environ Sci Pollut Res Int 2016; 23:20205-20213.
39. Calabrese V, Santoro A, Monti D, Crupi R, Paola R, Latteri S, et al. Aging and Parkinson’s disease: Inflammation, neuroinflammation and biological remodeling as key factors in pathogenesis. Free Radic Biol Med 2018; 115:80-91.
40. Wang J, Li N, Zheng L, Wang S, Wang Y, Zhao X,  et al. P38-Nrf-2 signaling pathway of oxidative stress in mice caused by nanoparticle TiO2. Biol Trace Elem Res 2011; 140:186-197.
41. Hauser DN, Hastings TG. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease and monogenic Parkinsonism. Neurobiol Dis 2013; 51:35-42.
42. Wu J, Xie H. Effects of titanium dioxide nanoparticles on α-synuclein aggregation and the ubiquitin-proteasome system in dopaminergic neurons. Artif Cells Nanomed Biotechnol 2016; 44:690-694.
43. Phillipson OT. Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic and circadian dysfunction in Parkinson’s disease. An integrated strategy for management. Ageing Res Rev 2017; 40:149-167.
44. Chen J, Dong X, Zhao J, Tang G. Acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection. J Appl Toxicol 2009; 29:330-337.
45. Hosseini M, Rajaei Z, Alaei H, Tajadini M. The effects of crocin on 6-OHDA-induced oxidative/nitrosative damage and motor behavior in hemiparkinsonian rats. Malays J Med Sci 2016; 23:35-43.
46. Garman RH. The return of the dark neuron. A histological artifact complicating contemporary neurotoxicologic evaluation. Neurotoxicology 2006; 27:1126-1137.
47. Gallyas F, Kiglics V, Baracskay P, Juhasz G, Czurko A. The mode of death of epilepsy-induced “dark” neurons is neither necrosis nor apoptosis: an electron-microscopic study. Brain Res 2008; 1239:207-215.
48. Hu R, Zheng L, Zhang T, Gao G, Cui Y, Cheng Z, et al. Molecular mechanism of hippocampal apoptosis of mice following exposure to titanium dioxide nanoparticles. J Hazard Mater 2011; 191:32-40.
49. Ebrahimzadeh-bideskan A, Mohammadipour A,  Fazel A, Haghir H, Rafatpanah H, Hosseini M, et al. Maternal exposure to titanium dioxide nanoparticles during pregnancy and lactation alters offspring hippocampal mRNA BAX and Bcl-2 levels, induces apoptosis and decreases neurogenesis. Exp Toxicol Pathol 2017; 69:329-337.
Iranian Journal of Basic Medical Sciences
Volume 22, Issue 7
July 2019
Pages 745-751

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