Examination of Acute Neurotoxic-Effect of Toluene on the Brain Cortex and Cerebellum Tissue: an experimental study

Abstract

The aim of this study is to examine the apoptotic effects of high-dose toluene on rat brain cortex and cerebellum tissues during the acute phase. Fourteen albino Wistar rats (180-200 g) were divided into two equal groups (n : 7). While Group I was used as a control group, Group II was applied to a high dose of toluene (5200 mg / kg / gavage). At the end of a three-hour experimental period brain tissue samples were taken from the killed animals and tissues were fixed in % 10 neutral formalin, then, embedded in paraffin and sectioned (thickness, 5 μm) to determine the immune reactivity of Bax, sections were stained immunohistochemically with avidin biotin-peroxidase method. At the same time the TUNEL method was used for detection of apoptosis in the brain cortex and cerebellum. As a result of the study, increased Bax immune reactivity was seen in the brain cortex (+++) and cerebellum (++++) of toluene treated rats compared to control. The numbers of TUNEL-positive cells were significantly higher in the cerebellum tissues of animals exposed to toluene than the control. Nevertheless there was not a significantly difference in terms of TUNEL positivity between the brain cortex of control and toluene exposed animals. As a result of this study it was shown that a high-dose of toluene can trigger apoptosis of the brain cortex and cerebellum in a very short period of time.

Keywords

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Examination of Acute Neurotoxic-Effect of Toluene on the Brain Cortex and Cerebellum Tissue: an experimental study

Öz

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Anahtar Kelimeler

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Kaynakça

1. Agency for Toxic Substances and Disease Registry (ATSDR) (2006) Case Studies in Environmental Medicine; Toluene Toxicity http://www.atsdr.cdc.gov/csem/toluene/docs/ toluene.pdf (accessed october 10, 2011).
2. Balster RL. Neural basis of inhalant abuse. Drug Alcohol Depend 1998;51:207-14.
3. Jones HE, Balster RL. Neurobehavioral consequences of intermittent prenatal exposure to high concentrations of toluene. Neurotoxicol Teratol 1997;19:305-13.
4. Filley CM, Halliday W, Kleinschmidt-DeMasters BK. The effects of toluene on the central nervous system. J Neuropathol Exp Neurol 2004;63:1-12.
5. Beyer CE, Stafford D, LeSage MG, Glowa JR, Steketee JD. Repeated exposure to inhaled toluene induces behavioral and neurochemical cross-sensitization to cocaine in rats. Psychopharmacology (Berl) 2001;154:198-204.
6. Park CK, Kwon KT, Lee DS, et al. [A case of toxic hepatitis induced by habitual glue sniffing]. Taehan Kan Hakhoe Chi 2003 ;9:332-6.
7. Faust RA. Chemical summary for toluene. 1994. http://www. epa.gov/chemfact/s_toluen.txt (accessed march 21, 2012).
8. Dossing M, Aelum JB, Hansen SH, Lundqvist GR, Andersen NT. Urinary hippuric acid and orthocresol excretion in man during experimental exposure to toluene. Br J Ind Med 1983;40:470-3.

9. OEHHA, Office of Environmental Health Hazard Assessment. 2004. Public health goals for chemicals in drinking water. http://www.oehha.org/water/phg/pdf/ perchlorate3docs.pdf (accessed January 21, 2012).
10. Tsatsakis AM, Dolapsakis G, Troulakis G, Christodoulou P, Relakis K, Trikilis N, et al. Fatal and non-fatal outcome by accidental intoxication with paint thinner. J Clin Forensic Med 1997;4:133-7.
11. Tomei F, Giuntoli P, Biagi M, Baccolo TP, Tomao E, Rosati MV. Liver damage among shoe repairers. Am J Ind Med 1999;36:541-7.
12. Argo A, Bongiorno D, Bonifacio A, Pernice V, Liotta R, Indelicato S, et al. A fatal case of a paint thinner inges- tion: comparison between toxicological and histological findings. Am J Forensic Med Pathol 2011;31:186-91.
13. Tan WP, Seow E. Case reports on acute toluene poison- ing during parquet flooring. Ann Acad Med Singapore 1997;26:138-40.
14. Kanter M. Protective effects of thymoquinone on the neu- ronal injury in frontal cortex after chronic toluene expo- sure. J Mol Histol 2011;42:39-46.
15. Gotohda T, Tokunaga I, Kubo S, Morita K, Kitamura O, Eguchi A. Effect of toluene inhalation on astrocytes and neurotrophic factor in rat brain. Forensic Sci Int 2000;113:233-8.
16. Baydas G, Ozveren F, Akdemir I, Tuzcu M, Yasar A. Learning and memory deficits in rats induced by chronic thinner exposure are reversed by melatonin. J Pineal Res 2005;39:50-6.
17. Seo HS, Yang M, Song MS, Kim JS, Kim SH, Kim JC, et al. Toluene inhibits hippocampal neurogenesis in adult mice. Pharmacol Biochem Behav 2010;94:588-94.
18. Hester SD, Johnstone AF, Boyes WK, Bushnell PJ, Shafer TJ. Acute toluene exposure alters expression of genes in the central nervous system associated with synaptic struc- ture and function. Neurotoxicol Teratol 2011;33:521-9.
19. Mehta CS, Sun PS, Zikarge A. Acute Toxicity of Toluene In Male and Female Rats: A Single Oral Dose Exposure 2-Week Study. Toxic Substance Mechanisms 1998;17:43-56.
20. Agency for Toxic Substances and Disease Registry (ATSDR) (2000) Toxicological Profile for Toluene, http://www. atsdr.cdc.gov/toxprofiles/tp56.pdf (accessed october 15, 2011).
21. Kanter M. Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats. Toxicol Ind Health 2011;27:387-95.
22. Pero RW. Health consequences of catabolic synthesis of hip- puric acid in humans. Curr Clin Pharmacol 2010;5:67-73.
23. El-Nabi Kamel MA, Shehata M. Effect of toluene exposure on the antioxidant status and apoptotic pathway in or- gans of the rat. Br J Biomed Sci 2008;65:75-9.
24. Gotohda T, Nishimura A, Morita K. Immunohistochemical studies on early stage of hepatic damage induced by sub- acute inhalation of toluene vapor in rats. J Appl Toxicol 2009;29:505-9.
25. Kanter M. Thymoquinone reestablishes spermatogenesis after testicular injury caused by chronic toluene exposure in rats. Toxicol Ind Health 2011;27:155-66.
26. Calderon-Guzman D, Espitia-Vazquez I, Lopez-Dominguez A, Hernandez-Garcia E, Huerta-Gertrudis B, Coballase- Urritia E, et al. Effect of toluene and nutritional status on serotonin, lipid peroxidation levels and NA+/K+-ATPase in adult rat brain. Neurochem Res 2005;30:619-24.
27. Bowen SE, Batis JC, Mohammadi MH, Hannigan JH. Abuse pattern of gestational toluene exposure and ear- ly postnatal development in rats. Neurotoxicol Teratol 2005;27:105-16.
28. Lee JI, Lee KS, Paik YH, Nyun Park Y, Han KH, Chon CY, et al. Apoptosis of hepatic stellate cells in carbon tetra- chloride induced acute liver injury of the rat: analysis of isolated hepatic stellate cells. J Hepatol 2003;39:960-6.
29. Tas U, Ogeturk M, Meydan S, Kus I, Kuloglu T, Ilhan N, et al. Hepatotoxic activity of toluene inhalation and protec- tive role of melatonin. Toxicol Ind Health 2011;27:465-73.
30. Saraste A, Pulkki K. Morphologic and biochemical hall- marks of apoptosis. Cardiovasc Res 2000;45:528-37.
31. Bender LM, Morgan MJ, Thomas LR, Liu ZG, Thorburn A. The adaptor protein TRADD activates distinct mechanisms of apoptosis from the nucleus and the cytoplasm. Cell Death Differ 2005;12:473-81.
32. Fulda S, Debatin KM. Resveratrol modulation of signal transduction in apoptosis and cell survival: a mini-review. Cancer Detect Prev 2006;30:217-23.
33. Win-Shwe TT, Yoshida Y, Kunugita N, Tsukahara S, Fujimaki H. Does early life toluene exposure alter the expres- sion of NMDA receptor subunits and signal transduction pathway in infant mouse hippocampus? Neurotoxicology 2010;31:647-53.
34. Tao XJ, Tilly KI, Maravei DV, Shifren JL, Krajewski S, Reed JC, et al. Differential expression of members of the bcl-2 gene family in proliferative and secretory human endo- metrium: Glandular epithelial cell apoptosis is associ- ated with increased expression of bax. Journal of Clinical Endocrinology & Metabolism 1997;82:2738-46.
35. D'Amelio M, Cavallucci V, Cecconi F. Neuronal cas- pase-3 signaling: not only cell death. Cell Death Differ 2010;17:1104-14.
36. Kanter M. Protective effects of Nigella sativa on the neu- ronal injury in frontal cortex and brain stem after chronic toluene exposure. Neurochem Res 2008;33:2241-9.
37. Baydas G, Reiter RJ, Nedzvetskii VS, Yasar A, Tuzcu M, Ozveren F, et al. Melatonin protects the central nervous system of rats against toluene-containing thinner intoxi- cation by reducing reactive gliosis. Toxicology Letters 2003;137:169-74.