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Current Nutrition & Food Science

Current Nutrition & Food Science

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ISSN (Print): 1573-4013
ISSN (Online): 2212-3881

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Research Article

The Effect of Sodium Metabisulphite on Apoptosis in the Experimental Model of Parkinson’s Disease

Author(s): Ayse Ozkan, Hande Parlak, Aysel Agar*, Özlem Özsoy, Gamze Tanriover, Sayra Dilmac, Eylem Turgut and Piraye Yargicoglu

Volume 16, Issue 3, 2020

Page: [296 - 305] Pages: 10

DOI: 10.2174/1573401314666180503153444

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Abstract

Background: The aim of this study was to investigate the mechanisms underlying possible toxic effects of sulphite on neurodegeneration.

Methods: Male Wistar rats were assigned to each of the four groups: Control (Control), Sulphite-treated (Sulphite), 6-hydroxydopamine (6-OHDA)-injected (6-OHDA), and sulphite-treated and 6-OHDA-injected (6-OHDA+Sulphite). Sodium metabisulphite was administered orally by gavage at a dose of 100 mg/kg/day for 45 days. Experimental PD was created stereotactically via the unilateral infusion of 6-OHDA into the medial forebrain bundle (MFB). Rotarod performances, plasma S-sulfonate levels, caspase-3 activities, Bax and Bcl-2 levels, tyrosine hydroxylase (TH) and cleaved caspase-3 double staining were investigated.

Results: The rotarod test showed that the 6-OHDA-injected animals exhibited shorter time on the rod mile compared to the control group; however, there was no difference between 6-OHDA and 6-OHDA+Sulphite groups. Plasma levels of S-sulfonate in Sulphite and 6-OHDA+ Sulphite groups increased in contrast to their corresponding control groups. Caspase-3 enzyme activity increased in the 6-OHDA group whereas it did not in control. However, sulphite treatment did not affect these activity levels. Anti-apoptotic protein Bcl-2 concentration decreased, but the concentration of pro-apoptotic protein Bax increased in the 6-OHDA group compared to the control group. The expression of caspase-3 increased, while the number of tyrosine hydroxylase (TH)-positive neurons decreased in 6-OHDA group as compared to the control groups. However, sulphite treatment had no effect on these parameters.

Conclusion: Sulphite is not a potentially aggravating factor for the activity of caspase-3 in a 6- OHDA-induced experimental model of Parkinson’s disease.

Keywords: 6-OHDA, bax, Bcl-2, caspase-3, Parkinson's disease, sulphite.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

[1]
Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002; 14(2): 223-36.
[http://dx.doi.org/10.1176/jnp.14.2.223] [PMID: 11983801]
[2]
Hornykiewicz O, Kish SJ. Biochemical pathophysiology of Parkinson’s disease. Adv Neurol 1987; 45: 19-34.
[PMID: 2881444]
[3]
McGeer PL, Itagaki S, Akiyama H, McGeer EG. Rate of cell death in parkinsonism indicates active neuropathological process. Ann Neurol 1988; 24(4): 574-6.
[http://dx.doi.org/10.1002/ana.410240415] [PMID: 3239957]
[4]
Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39(6): 889-909.
[http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID: 12971891]
[5]
Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 2005; 28: 57-87.
[http://dx.doi.org/10.1146/annurev.neuro.28.061604.135718] [PMID: 16022590]
[6]
Adams JD Jr, Chang ML, Klaidman L. Parkinson’s disease--redox mechanisms. Curr Med Chem 2001; 8(7): 809-14.
[http://dx.doi.org/10.2174/0929867013372995] [PMID: 11375751]
[7]
Cohen GM, d’Arcy Doherty M. Free radical mediated cell toxicity by redox cycling chemicals. Br J Cancer Suppl 1987; 8: 46-52.
[PMID: 2820459]
[8]
Graham DG. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 1978; 14(4): 633-43.
[PMID: 98706]
[9]
Ben-Shachar D, Eshel G, Finberg JP, Youdim MB. The iron chelator desferrioxamine (Desferal) retards 6-hydroxydopamine-induced degeneration of nigrostriatal dopamine neurons. J Neurochem 1991; 56(4): 1441-4.
[http://dx.doi.org/10.1111/j.1471-4159.1991.tb11444.x] [PMID: 1900527]
[10]
Andersen JK, Frim DM, Isacson O, Beal MF, Breakefield XO. Elevation of neuronal MAO-B activity in a transgenic mouse model does not increase sensitivity to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Brain Res 1994; 656(1): 108-14.
[http://dx.doi.org/10.1016/0006-8993(94)91371-4] [PMID: 7804823]
[11]
Graham DG. Catecholamine toxicity: a proposal for the molecular pathogenesis of manganese neurotoxicity and Parkinson’s disease. Neurotoxicology 1984; 5(1): 83-95.
[PMID: 6538951]
[12]
Choi WS, Eom DS, Han BS, et al. Phosphorylation of p38 MAPK induced by oxidative stress is linked to activation of both caspase-8- and -9-mediated apoptotic pathways in dopaminergic neurons. J Biol Chem 2004; 279(19): 20451-60.
[http://dx.doi.org/10.1074/jbc.M311164200] [PMID: 14993216]
[13]
Przedborski S. Pathogenesis of nigral cell death in Parkinson’s disease. Parkinsonism Relat Disord 2005; 11(Suppl. 1): S3-7.
[http://dx.doi.org/10.1016/j.parkreldis.2004.10.012] [PMID: 15885625]
[14]
Saito Y, Nishio K, Ogawa Y, et al. Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: involvement of hydrogen peroxide-dependent and -independent action. Free Radic Biol Med 2007; 42(5): 675-85.
[http://dx.doi.org/10.1016/j.freeradbiomed.2006.12.004]
[15]
Cryns V, Yuan J. Proteases to die for. Genes Dev 1998; 12(11): 1551-70.
[http://dx.doi.org/10.1101/gad.12.11.1551] [PMID: 9620844]
[16]
Tatton NA. Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease. Exp Neurol 2000; 166(1): 29-43.
[http://dx.doi.org/10.1006/exnr.2000.7489] [PMID: 11031081]
[17]
Baraka AM, Korish AA, Soliman GA, Kamal H. The possible role of estrogen and selective estrogen receptor modulators in a rat model of Parkinson’s disease. Life Sci 2011; 88(19-20): 879-85.
[http://dx.doi.org/10.1016/j.lfs.2011.03.010] [PMID: 21420980]
[18]
Han BS, Noh JS, Gwag BJ, Oh YJ. A distinct death mechanism is induced by 1-methyl-4-phenylpyridinium or by 6-hydroxydopamine in cultured rat cortical neurons: degradation and dephosphorylation of tau. Neurosci Lett 2003; 341(2): 99-102.
[http://dx.doi.org/10.1016/S0304-3940(03)00173-3] [PMID: 12686375]
[19]
Hartmann A, Michel PP, Troadec JD, et al. Is Bax a mitochondrial mediator in apoptotic death of dopaminergic neurons in Parkinson’s disease? J Neurochem 2001; 76(6): 1785-93.
[http://dx.doi.org/10.1046/j.1471-4159.2001.00160.x] [PMID: 11259496]
[20]
Gokirmak M, Yildirim Z, Canan Hasanoglu H, Koksal N, Mehmet N. The role of oxidative stress in bronchoconstriction due to occupational sulfur dioxide exposure. Clin Chim Acta 2003; 331(1-2): 119-26.
[http://dx.doi.org/10.1016/S0009-8981(03)00117-7] [PMID: 12691872]
[21]
Haider SS. Effects of exhaust pollutant sulfur dioxide on lipid metabolism of guinea pig organs. Ind Health 1985; 23(2): 81-7.
[http://dx.doi.org/10.2486/indhealth.23.81] [PMID: 4055439]
[22]
Inouye B, Morita K, Ishida T, Ogata M. Cooperative effect of sulfite and vanadium compounds on lipid peroxidation. Toxicol Appl Pharmacol 1980; 53(1): 101-7.
[http://dx.doi.org/10.1016/0041-008X(80)90386-5] [PMID: 7385229]
[23]
Shi X, Mao Y. 8-Hydroxy-2′-deoxyguanosine formation and DNA damage induced by sulfur trioxide anion radicals. Biochem Biophys Res Commun 1994; 205(1): 141-7.
[http://dx.doi.org/10.1006/bbrc.1994.2641] [PMID: 7999014]
[24]
Cooper AJ. Biochemistry of sulfur-containing amino acids. Annu Rev Biochem 1983; 52: 187-222.
[http://dx.doi.org/10.1146/annurev.bi.52.070183.001155]
[25]
Yang WH, Purchase EC. Adverse reactions to sulfites. CMAJ 1985; 133(9): 865-867, 880.
[PMID: 4052897]
[26]
Altland K, Winter P. Potential treatment of transthyretin-type amyloidoses by sulfite. Neurogenetics 1999; 2(3): 183-8.
[http://dx.doi.org/10.1007/s100480050081] [PMID: 10541593]
[27]
Karoui H, Hogg N, Fréjaville C, Tordo P, Kalyanaraman B. Characterization of sulfur-centered radical intermediates formed during the oxidation of thiols and sulfite by peroxynitrite. ESR-spin trapping and oxygen uptake studies. J Biol Chem 1996; 271(11): 6000-9.
[http://dx.doi.org/10.1074/jbc.271.11.6000] [PMID: 8626383]
[28]
Mottley C, Mason RP. Sulfate anion free radical formation by the peroxidation of (Bi)sulfite and its reaction with hydroxyl radical scavengers. Arch Biochem Biophys 1988; 267(2): 681-9.
[http://dx.doi.org/10.1016/0003-9861(88)90077-X] [PMID: 2850769]
[29]
Derin N, Yargiçoğlu P, Aslan M, Elmas O, Agar A, Aicigüzel Y. The effect of sulfite and chronic restraint stress on brain lipid peroxidation and anti-oxidant enzyme activities. Toxicol Ind Health 2006; 22(6): 233-40.
[http://dx.doi.org/10.1191/0748233706th264oa] [PMID: 16924954]
[30]
Küçükatay V, Hacioğlu G, Savcioğlu F, Yargiçoğlu P, Ağar A. Visual evoked potentials in normal and sulfite oxidase deficient rats exposed to ingested sulfite. Neurotoxicology 2006; 27(1): 93-100.
[http://dx.doi.org/10.1016/j.neuro.2005.07.002] [PMID: 16150492]
[31]
Bai J, Meng Z. Expression of caspase and apoptotic signal pathway induced by sulfur dioxide. Environ Mol Mutagen 2010; 51(2): 112-22.
[http://dx.doi.org/10.1002/em.20517] [PMID: 19621461]
[32]
Sang N, Yun Y, Yao GY, Li HY, Guo L, Li GK. SO(2)-induced neurotoxicity is mediated by cyclooxygenases-2-derived prostaglandin E(2) and its downstream signaling pathway in rat hippocampal neurons. Toxicol Sci 2011; 124(2): 400-13.
[http://dx.doi.org/10.1093/toxsci/kfr224] [PMID: 21873648]
[33]
Heafield MT, Fearn S, Steventon GB, Waring RH, Williams AC, Sturman SG. Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson’s and Alzheimer’s disease. Neurosci Lett 1990; 110(1-2): 216-20.
[http://dx.doi.org/10.1016/0304-3940(90)90814-P] [PMID: 2325885]
[34]
McFadden SA. Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. Toxicology 1996; 111(1-3): 43-65.
[http://dx.doi.org/10.1016/0300-483X(96)03392-6] [PMID: 8711748]
[35]
Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JP. Environmental risk factors and Parkinson’s disease: An umbrella review of meta-analyses. Parkinsonism Relat Disord 2016; 23: 1-9.
[http://dx.doi.org/10.1016/j.parkreldis.2015.12.008] [PMID: 26739246]
[36]
Costello S, Cockburn M, Bronstein J, Zhang X, Ritz B. Parkinson’s disease and residential exposure to maneb and paraquat from agricultural applications in the central valley of California. Am J Epidemiol 2009; 169(8): 919-26.
[http://dx.doi.org/10.1093/aje/kwp006] [PMID: 19270050]
[37]
Sang N, Hou L, Yun Y, Li G. SO(2) inhalation induces protein oxidation, DNA-protein crosslinks and apoptosis in rat hippocampus. Ecotoxicol Environ Saf 2009; 72(3): 879-84.
[http://dx.doi.org/10.1016/j.ecoenv.2008.07.007] [PMID: 18722661]
[38]
Yun Y, Li H, Li G, Sang N. SO2 inhalation modulates the expression of apoptosis-related genes in rat hippocampus via its derivatives in vivo. Inhal Toxicol 2010; 22(11): 919-29.
[http://dx.doi.org/10.3109/08958378.2010.494694] [PMID: 20545484]
[39]
Cheng B, Yang X, Hou Z, et al. D-beta-hydroxybutyrate inhibits the apoptosis of PC12 cells induced by 6-OHDA in relation to up-regulating the ratio of Bcl-2/Bax mRNA. Auton Neurosci 2007; 134(1-2): 38-44.
[http://dx.doi.org/10.1016/j.autneu.2007.02.002] [PMID: 17369104]
[40]
Lashuel HA, Petre BM, Wall J, et al. Alpha-synuclein, especially the Parkinson’s disease-associated mutants, forms pore-like annular and tubular protofibrils. J Mol Biol 2002; 322(5): 1089-102.
[http://dx.doi.org/10.1016/S0022-2836(02)00735-0] [PMID: 12367530]
[41]
Niranjan R. The role of inflammatory and oxidative stress mechanisms in the pathogenesis of Parkinson’s disease: focus on astrocytes. Mol Neurobiol 2014; 49(1): 28-38.
[http://dx.doi.org/10.1007/s12035-013-8483-x] [PMID: 23783559]
[42]
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997; 388(6645): 839-40.
[http://dx.doi.org/10.1038/42166] [PMID: 9278044]
[43]
Blum D, Torch S, Lambeng N, et al. Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 2001; 65(2): 135-72.
[http://dx.doi.org/10.1016/S0301-0082(01)00003-X] [PMID: 11403877]
[44]
Ungerstedt U. 6-Hydroxy-dopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 1968; 5(1): 107-10.
[http://dx.doi.org/10.1016/0014-2999(68)90164-7] [PMID: 5718510]
[45]
Ungerstedt U, Arbuthnott GW. Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system. Brain Res 1970; 24(3): 485-93.
[http://dx.doi.org/10.1016/0006-8993(70)90187-3] [PMID: 5494536]
[46]
Hökfelt T, Ungerstedt U. Specificity of 6-hydroxydopamine induced degeneration of central monoamine neurones: an electron and fluorescence microscopic study with special reference to intracerebral injection on the nigro-striatal dopamine system. Brain Res 1973; 60(2): 269-97.
[http://dx.doi.org/10.1016/0006-8993(73)90791-9] [PMID: 4763613]
[47]
Truong L, Allbutt H, Kassiou M, Henderson JM. Developing a preclinical model of Parkinson’s disease: a study of behaviour in rats with graded 6-OHDA lesions. Behav Brain Res 2006; 169(1): 1-9.
[http://dx.doi.org/10.1016/j.bbr.2005.11.026] [PMID: 16413939]
[48]
FAO/WHO. Expert Comittee of Food Additives Food Additives with a Review of General Principle and of Specifications. Food and Agriculture Organization 1974.
[49]
Til HP, Feron VJ, De Groot AP. The toxicity of sulphite. I. Long-term feeding and multigeneration studies in rats. Food Cosmet Toxicol 1972; 10(3): 291-310.
[http://dx.doi.org/10.1016/S0015-6264(72)80250-5] [PMID: 5045676]
[50]
Gunnison AF, Jacobsen DW. Sulfite hypersensitivity. A critical review. CRC Crit Rev Toxicol 1987; 17(3): 185-214.
[http://dx.doi.org/10.3109/10408448709071208] [PMID: 3556020]
[51]
Taylor SL, Higley NA, Bush RK. Sulfites in foods: uses, analytical methods, residues, fate, exposure assessment, metabolism, toxicity, and hypersensitivity. Adv Food Res 1986; 30: 1-76.
[http://dx.doi.org/10.1016/S0065-2628(08)60347-X] [PMID: 3526827]
[52]
Ozsoy O, Yildirim FB, Ogut E, et al. Melatonin is protective against 6-hydroxydopamine-induced oxidative stress in a hemiparkinsonian rat model. Free Radic Res 2015; 49(8): 1004-14.
[http://dx.doi.org/10.3109/10715762.2015.1027198] [PMID: 25791066]
[53]
Ozturk N, Yargicoglu P, Derin N, Akpinar D, Agar A, Aslan M. Dose-dependent effect of nutritional sulfite intake on visual evoked potentials and lipid peroxidation. Neurotoxicol Teratol 2011; 33(2): 244-54.
[http://dx.doi.org/10.1016/j.ntt.2010.09.002] [PMID: 20875852]
[54]
Nair B, Elmore AR, Cosmetic Ingredients Review Expert P. Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite. Int J Toxicol 2003; 22(Suppl. 2): 63-88.
[http://dx.doi.org/10.1080/10915810305077X] [PMID: 14555420]
[55]
Green LF. Sulphur dioxide and food preservation-a review. Food Chem 1976; 1(2): 103-24.
[http://dx.doi.org/10.1016/0308-8146(76)90003-0]
[56]
Gunnison AF, Sellakumar A, Currie D, Snyder EA. Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats. J Toxicol Environ Health 1987; 21(1-2): 141-62.
[http://dx.doi.org/10.1080/15287398709531008] [PMID: 3573068]
[57]
Kucukatay V, Savcioglu F, Hacioglu G, et al. Effect of sulfite on cognitive function in normal and sulfite oxidase deficient rats. Neurotoxicol Teratol 2005; 27(1): 47-54.
[http://dx.doi.org/10.1016/j.ntt.2004.10.002]
[58]
Gambhir H, Mathur R, Behari M. Progressive impairment in motor skill learning at 12 and 20 weeks post 6-OHDA- SNc lesion in rats. Parkinsonism Relat Disord 2011; 17(6): 476-8.
[http://dx.doi.org/10.1016/j.parkreldis.2010.12.017] [PMID: 21367640]
[59]
Tyurina YY, Tyurin VA, Carta G, Quinn PJ, Schor NF, Kagan VE. Direct evidence for antioxidant effect of Bcl-2 in PC12 rat pheochromocytoma cells. Arch Biochem Biophys 1997; 344(2): 413-23.
[http://dx.doi.org/10.1006/abbi.1997.0201] [PMID: 9264556]
[60]
Shimizu S, Narita M, Tsujimoto Y. Bcl-2 family proteins regulate the release of apoptogenic cytochrome c by the mitochondrial channel VDAC. Nature 1999; 399(6735): 483-7.
[http://dx.doi.org/10.1038/20959] [PMID: 10365962]
[61]
Earnshaw WC, Martins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 1999; 68: 383-424.
[http://dx.doi.org/10.1146/annurev.biochem.68.1.383] [PMID: 10872455]
[62]
Feng L, Meng H, Wu F, et al. Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways. Int J Dev Neurosci 2008; 26(3-4): 323-9.
[http://dx.doi.org/10.1016/j.ijdevneu.2008.01.003]
[63]
Kramer BC, Mytilineou C. Alterations in the cellular distribution of bcl-2, bcl-x and bax in the adult rat substantia nigra following striatal 6-hydroxydopamine lesions. J Neurocytol 2004; 33(2): 213-23.
[http://dx.doi.org/10.1023/B:NEUR.0000030696.62829.ec] [PMID: 15322379]
[64]
Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74(4): 609-19.
[http://dx.doi.org/10.1016/0092-8674(93)90509-O] [PMID: 8358790]
[65]
Youdim MB, Amit T, Falach-Yogev M, Bar Am O, Maruyama W, Naoi M. The essentiality of Bcl-2, PKC and proteasome-ubiquitin complex activations in the neuroprotective-antiapoptotic action of the anti-Parkinson drug, rasagiline. Biochem Pharmacol 2003; 66(8): 1635-41.
[http://dx.doi.org/10.1016/S0006-2952(03)00535-5] [PMID: 14555244]
[66]
Yun Y, Hou L, Sang N. SO(2) inhalation modulates the expression of pro-inflammatory and pro-apoptotic genes in rat heart and lung. J Hazard Mater 2011; 185(1): 482-8.
[http://dx.doi.org/10.1016/j.jhazmat.2010.09.057] [PMID: 20951496]
[67]
Xie J, Li R, Fan R, Meng Z. Effects of sulfur dioxide on expressions of p53, bax and bcl-2 in lungs of asthmatic rats. Inhal Toxicol 2009; 21(11): 952-7.
[http://dx.doi.org/10.1080/08958370802629602] [PMID: 19681733]
[68]
Li H, Zhu H, Xu CJ, Yuan J. Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis. Cell 1998; 94(4): 491-501.
[http://dx.doi.org/10.1016/S0092-8674(00)81590-1] [PMID: 9727492]
[69]
Ozsoy O, Tanriover G, Derin N, et al. The effect of docosahexaenoic Acid on visual evoked potentials in a mouse model of Parkinson’s disease: the role of cyclooxygenase-2 and nuclear factor kappa-B. Neurotox Res 2011; 20(3): 250-62.
[http://dx.doi.org/10.1007/s12640-011-9238-y] [PMID: 21234736]

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