EBSELEN PROTECTS AGAINST OXIDATIVE AND MORPHOLOGICAL EFFECTS OF HIGH CONCENTRATION CHRONIC TOLUENE EXPOSURE ON RAT SCIATIC NERVES

Abstract

-

Keywords

• -

EBSELEN PROTECTS AGAINST OXIDATIVE AND MORPHOLOGICAL EFFECTS OF HIGH CONCENTRATION CHRONIC TOLUENE EXPOSURE ON RAT SCIATIC NERVES

Abstract

Aim: Neuroprotective effects of ebselen against free radical damage have been studied extensively. Toluene generates reactive oxygen species (ROS) and the toxic effects relating to these reactants. The aim of this study was designed to investigate the effects of chronic toluene inhalation in high concentration on lipid peroxidation, antioxidant enzyme activities and ultrastructural changes in the sciatic nerves of rats. Methods: We also examined the protective effects of ebselen against toluen exposure. Male Wistar albino rats (150-250 g) were divided in three experimental groups: the control, toluene and toluene+ebselen treated group (n=10 for each). Toluene treatment was performed by inhalation of 3000 ppm toluene, in a 8 hr/day and 6 day/week order for 16 weeks. Control group received 1ml serum physiologic and ebselen was given i.p. (10 mg/kg) to toluene+ebselen treated group just after toluene exposure per day. Blood and tissue samples were obtained for biochemical and histopathological investigation. The blood and sciatic nerves were assayed for toluene by gas chromatography. Results: Toluene significantly increased blood and tissue malondialdehyde (MDA), and decreased tissue superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but not tissue catalase (CAT) levels when compared with controls. Ebselen administration prevented to increase of blood and tissue MDA and decrease to SOD and GSH-Px levels induced by toluene inhalation. Electron micrographs of sciatic nerve in the toluene group shows myelin destructions with onion-bulb and bubble form protrusion on the myelin sheath and axolemma border of myelinated axons. Furthermore, ebselen salvaged the nerve fibers from toluene exposure. Conclusion: Ebselen treatment may provide neuroprotection against toluene neurotoxicity by directly scavenging ROS and by indirectly augmenting their antioxidant capacity. Key words: Toluene, ebselen, lipid peroxidation, antioxidant enzymes, ultrastructural, sciatic nerve

Keywords

• Toluene, ebselen, lipid peroxidation, antioxidant enzymes, ultrastructural, sciatic nerve

References

1. Bergamaschi E, Smargiassi A, Mutti A et al. Peripheral markers of catecholaminergic symptoms of neurotoxicity among styrene-exposed workers. Int. Arch. Occup Environ Health 1997;69(3):209- 14 dysfunction and
2. Benignus VA, Muller KE, Barton CN, Bittikofer JA. Toluene levels in blood and brain of rats during and after respiratory exposure. Toxicol Appl Pharmacol 1981; 61(3):326-34
3. Greenberg MM. The central nervous system and exposure to toluene: a risk characterization. Environ Res 1997;72(1): 1-7
4. Pryor GT, Rebert CS, Howd RA. Hearing loss in rats caused by inhalation of mixed xylenes and styrene. J Appl Toxicol 1987; 7:55-61
5. Crofton KM, Lassiter TL, Rebert CS. Solvent-induced ototoxicity in rats: an atypical selective mid-frequency hearing deficit. Hear Res 1994;80(1):25-30
6. Campagna D, Stengel B, Mergler D et al. Color vision and occupational toluene exposure. Neurotoxicol Teratol 2001; 23(5):473-80
7. Balster RL. Neural basis of inhalant abuse. Drug Alcohol Depend 1998;51: 207-14
8. Moser VC, Balster RL. The effects of inhaled toluene, halothane, 1,1,1,- trichloroethane, and ethanol on fixed- interval responding in mice. Neurobehav. Toxicol Teratol 1986;8(5):525-31

9. Warren DA, Bowen SE, Jennings WB, Dallas CE, Balster RL. Biphasic effects of 1,1,1-trichloroethane on the locomotor activity of mice: relationship to blood and brain solvent concentrations. Toxicol Sci 2000;56(2):365-73
10. Tegeris JS, Balster RL. A comparison of the acute behavioral effects of alkylbenzenes observational battery in mice. Fundam Appl Toxicol 1994;22(2):240-50
11. Echeverria D, Fine L, Langolf G, Schork T, Sampaio C. Acute behavioral comparisons of toluene and ethanol in human subjects. Br J Ind Med 1991;48(11):750-61
12. Mattia CJ, Adams JD, Jr Bondy SC. Free radical induction in the brain and liver by products of toluene catabolism. Biochem Pharmacol 1993;46(1):103-10
13. Zabedah MY, Razak M, Zakiak I, Zuraidah AB. Profile of solvent abusers (glue sniffers) in East Malaysia. Malays J Pathol 2001;23(2):105–9
14. Müller A, Cadenas E, Graf P, Sies H. A novel biologically active selenoorganic- compound, I: Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ51 (Ebselen). Biochem Pharmacol 1984;33(20):3235–9
15. Dawson DA, Masayasu H, Graham DI, Macrae IM. The neuroprotective efficacy of ebselen (a glutathione peroxidase mimic) on brain damage induced by transient focal cerebral ischaemia in the rat. Neurosci Lett 1995;185(1):65–9
16. Takasago T, Peters EE, Graham DI, Masayasu H, Macrae IM. Neuroprotective efficacy of ebselen, an anti-oxidant with anti-inflammatory actions, in a rodent model of permanent middle cerebral artery occlusion. Br J Pharmacol 1997;122(6):1251–6
17. Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1990; 186:421-31
18. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497–500
19. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterisation glutathione peroxidase. J Lab Clin Med 1967;70(1):158-69 of erythrocyte
20. Aebi H. Catalase. In: Bergmeyer HU, editor. Methods of enzymatic analysis. New York: Academic Press 1974. 673-7
21. Lowry OH, Rosebrough NJ, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193: 265-72
22. Sunderland S. Nerves and nerve injuries, (3rd ed.) Melbourne, Australia: Churchill Livingstone, 1978
23. Kaye A.“Classification of Nerve Injuries” in Essential Neurosurgery. Churchill Livingstone. 1991, 333-334
24. Keane JR. Toluene optic neuropathy. Ann Neurol 1978;4:390
25. Toyonaga N, Adachi-Usami E, Asanagi K, Takasoh M. Electrophysiological studies on visual toxicity of toluene. Nippon Ganka Gakkai Zasshi 1988;92(11): 1875- 80
26. Burmistrov, S.O., A.V., Stepanov, M.G., Oparina, T.I., Prokopenko, V.M., 2001. Effect of chronic inhalation of toluene and dioxane on activity of free radical processes in rat ovaries and brain. Bull Exp Biol Med 132(3), 832-836 Arutyunyan, 27. HESD Publication No: 28-31210. Twenty-six week inhalation toxicity study of toluene in the rat. Washington, DC, American Petroleum Institute, 1981
27. Naalsund LU. Changes in neurobiological parameters in the brain after toluene inhalation. Second Nordic Neurochemical Symposium, Copenhagen, 1985, August 21–5
28. Savolainen H. Superoxide dismutase and glutathione peroxidase activities in rat brain. Res. Commun. Chem. Pathol Pharmacol 1978;21(1):173-6
29. Raps SP, Lai JC, Hertz L, Cooper AJ. Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons. Brain Res 1989; 493:398-401
30. Castagne V, Gautschi M, Lefevre K, Posada A, Clarke PG. Relationships between neuronal death and the cellular redox status. Focus on the developing nervous 1999;59(4):397–423 Progr Neurobiol
31. Ursini F, Maiorino M, Brigelius-Flohe R et al. Diversity of glutathione peroxidases. Methods Enzymol 1995;252:38–53
32. Sies H. Ebselen, a selenoorganic compound as glutathione peroxidase mimic. Free Radic Biol Med 1993;14: 313–23 34. Bukowski JA. Review of the epidemiological evidence relating toluene to reproductive outcomes. Regul Toxicol Pharmacol 2001;33(2):147–56
33. Bruckner JV, Peterson RG. Evaluation of toluene and acetone inhalant abuse. II. Model development and toxicology. Toxicol Appl Pharmacol 1981;61:302–12
34. Lizumi H, Fukui K, Utsumi H, Kawashima Y, Nakajima T. Effect of chronic toluene exposure on tyrosine hydroxylase-positive nerve elements in the rat forebrain: an immunohistochemical study combined with semiquantitative morphometric analysis. Neuroreport 1995;7:81-4
35. Barroso-Moguel R, Villeda Hernandez J. Experimental neuropathy produced in rats with industrial solvents (thinner). Arch Invest Med 1989;20(1):53-60
36. Baydas G, Reiter RJ, Nedzvetskii VS et al. Melatonin protects the central nervous system of rats against toluene-containing thinner intoxication by reducing reactive gliosis. Toxicol Lett 2003;137(3):169-74
37. Altenkirch H, Mager J, Stoltenburg G, Helmbrecht J. Toxic polyneuropathies after sniffing a glue thinner. J Neurol 1977;214:137-52
38. Gate L, Paul J, Ba GN, Tew KD, Tapiero H. Oxidative stress induced in pathologies: the role of antioxidants. Biomed Pharmacother 1999;53(4):169– 80
39. Oh TJ. Kim IG, Park SY, Kim CK, Shim HW. NAD-dependent malate dehydrogenase protects against oxidative damage in Escherichia coli K-12 through the action of oxaloacetate. Environ Toxicol Pharmacol 2002;11:9-14
40. Cnubben NHP, Ivonne MCM. Rietjens WH, van Zanden J, van Bladeren PJ. The interplay of glutathione-related processes in antioxidant defense. Environ Toxicol Pharmacol 2001;10(4):141–52
41. Bhatia AL, Manda K. Study on pre- treatment of melatonin against radiation- induced oxidative stress in mice. Environ Toxicol Pharmacol 2004;18(1):13–20
42. Cotgreave IA, Johansson U, Westergren G, Moldeus PW, Brattsand R. The anti- inflammatory activity of ebselen but not thiols in experimental alveolitis and bronchiolitis. Agents Actions 1988;24(3- 4):313–9
43. Rocha JBT, Gabriel D, Zeni G et al. Ebselen and diphenyl diselenide change biochemical overdosage with paracetamol. Environ Toxicol Pharmacol 2005;19:255–61 to