Abstract
Monosodium glutamate (MSG) is a natural constituent of many foods and was reported to have neurotoxic effects. The aim of this study was to investigate the possible toxic effect of MSG on histological and glial fibrillary acidic protein (GFAP) immunohistochemical features of cerebellar cortex of albino rats and to evaluate the possible protective role of vitamin C against this effect. Thirty rats were divided into 3 equal groups. Group I, control; Group II, treated with 3 g/kg/day of MSG and Group III, received 100 mg/kg/day of vitamin C simultaneously with MSG. After 14 days, cerebellar tissues were obtained and processed to prepare sections stained with H&E, toluidine blue. The GFAP was detected immunohistochemically. Histological examination of group II showed degenerative changes as pyknotic Purkinje and granule cells with areas of degeneration surrounded by inflammatory cells in granular layer. However, group III showed more preserved histological structure of cerebellar cortex. Statistical analysis of area percent of the GFAP immunoreaction among studied groups showed significant increase in group III when compared with group I and group II. However, a non significant increase was detected in group II when compared with group I. In conclusion, MSG has neurotoxic effect leading to degenerative changes in neurons and astrocytes in cerebellar cortex of albino rats and vitamin C supplementation could protect from these changes. Getting more attention to the constituents of food products is recommended and vitamin C could be advised to protect people from food oxidants additives.
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Audebert M, Charbonnier JB, Boiteux S, Radicella JP (2002) Mitochondrial targeting of human 8-oxoguanine DNA glycosylase hOGG1 is impaired by a somatic mutation found in kidney cancer. DNA Repair (Amst) 17:497–505
Babai N, Atlasz T, Tamás A, Regl D, Tóth G, Kiss P, Gábriel R (2006) Search for the optimal monosodium glutamate treatment schedule to study the neuroprotective effects of PACAP in the retina. Annals 1070:149–155 (Abstract)
Bancroft JD, Gamble M (2002) Theory and practice of histological techniques. Churchill Livingstone, London
Baydas G, Ozer M, Yasar A, Koz ST, Tuzcu M (2006) Melatonin prevents oxidative stress and inhibits reactive gliosis induced by hyperhomocysteinemia in rats. Biochemistry (Mosc) 71:91–95
Bocci G, Fasciani A, Danesi R, Viacava P, Genazzani AR, Del Tacca M (2001) In vitro evidence of autocrine secretion of vascular endothelial growth factor by endothelial cells from human placental blood vessels. Mol Hum Reprod 7:771–777
Bojanic VV, Bojanic Z, Najman S, Ivanov-èurlis J, Tomin J, Dinoic B, Savic T (2004) Diltiazem prevention of monosodium glutamate toxicity on hypothalamus in Wistar rats. Arch Oncol 12:19–20
Calabresi P, Centonze D, Paolo G, Marfia GA, Bernardi G (1999) Glutamate-triggered events inducing corticostriatal long-term depression. J Neurosci 19:6102–6110
Chen CJ, Liao SL, Kuo JS (2000) Gliotoxic action of glutamate on cultured astrocytes. J Neurochem 75:1557–1565
Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105
Daniels M, Brown DR (2001) Astrocytes regulate N-methyl-D-aspartate receptor subunit composition increasing neuronal sensitivity to excitotoxicity. J Biol Chem 276:22446–22452
Dawson EB, Evans DR, Harris WA, Teter MC, McGanity WJ (1999) The effect of ascorbic acid supplementation on the blood lead levels of smokers. J Am Coll Nutr 18:166–170
Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267:4912–4916
Eweka AO, Om’Iniabohs FAE (2007) Histological studies of the effects of monosodium glutamate on the cerebellum of adult wistar rats. Internet J Neurol 8 (http://www.ispub.com)
Eweka AO, Om’Iniabohs FAE (2008) Histological studies of the effects of monosodium glutamate on the inferior colliculus of adult wistar rats. Rev Electron Biomed Electron J Biomed 3:24–30
Farombi EO, Onyema OO (2006) Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: modulatory role of vitamin C, vitamin E and quercetin. Hum Exp Toxicol 25:251–259
Gallo V, Ciotti MT, Coletti A, Aloisi F, Levi G (1982) Selective release of glutamate from cerebellar granule cells differentiating in culture. Proc Natl Acad Sci USA 79:7919–7923
Ganong WF (2005) Circulation through special organs. In: Review of medical physiology, chap 32. McGraw-Hill, New York, pp 611–630
Geha RS, Beiser A, Ren C, Patterson R, Paul A, Greenberger PA, Leslie C, Grammer LC, Ditto AM, Harris KE, Shaughnessy MA, Yarnold PR, Corren J, Saxon A (2000) Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. J Nutr 130:1058S–1062S
Giffard RG, Swanson RA (2005) Ischemia-induced programmed cell death in astrocytes. Glia 50:299–306
Gill SS (2000) Potential target sites in peripheral tissues for excitatory neurotransmission and excitotoxicity. Toxicol Pathol 28:277–284
Giordano G, Kavanagh TJ, Costa LG (2009) Mouse cerebellar astrocytes protect cerebellar granule neurons against toxicity of the polybrominated diphenyl ether (PBDE) mixture DE-71. NeuroToxicology 30:326–329
Glauret AM, Lewis PR (1998) Biological specimen preparation for transmission electron microscopy. Portlant, London
Goldsmith PC (2000) Neuroglial responses to elevated glutamate in the medial basal hypothalamus of the infant mouse. J Nutr 130:1032S–1038S
Gonzalez M (1990) Ascorbic acid and selenium interaction: its relevance in carcinogenesis. J Orthomol Med 5:67–69
Hanbury R, Ling ZD, Wuu J, Jeffrey K (2003) GFAP knockout mice have increased levels of GDNF that protect striatal neurons from metabolic and excitotoxic insults. J Comp Neurol 461:307–316
Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27:735–743
Higashino H, Niwa A, Satou T, Ohta Y, Hashimoto S, Tabuchi M, Ooshima K (2009) Immunohistochemical analysis of brain lesions using S100B and glial fibrillary acidic protein antibodies in arundic acid-(ONO-2506) treated stroke-prone spontaneously hypertensive rats. J Neural Trans 116:1209–1219
Hughes EG, Maguire JL, McMinn MT, Scholz RE, Sutherland ML (2004) Loss of glial fibrillary acidic protein results in decreased glutamate transport and inhibition of PKA-induced EAAT2 cell surface trafficking. Brain Res Mol Brain Res 124:114–123
Jiang SX, Lertvorachon J, Hou ST, Konishi Y, Webster J, Mealing G, Brunette E, Tauskela J, Preston E (2005) Chlortetracycline and demeclocycline inhibit calpains and protect mouse neurons against glutamate toxicity and cerebral ischemia. J Biol Chem 280:33811–33818
Kiernan JA (1999) Histological and histochemical methods: theory and practice. Butterworth-Heinemann, Oxford
Li ZY, Tso MO, Wong H, Organisciak DT (1985) Amelioration of photic injury in rat retina by ascorbic acid: a histopathologic study. Investig Ophthalmol Vis Sci 26:1589–1598
Loo BV, Bachschmid M, Spitzer V, Brey L, Ullrich V, Luscher TF (2003) Decreased plasma and tissue levels of vitamin C in a rat model of aging: implications for antioxidative defense. Biochem Biophys Res Commun 303:483–487
Magistretti PJ, Ransom BR (2002) Astrocytes. In: Davis KL, Charney D, Coyle JT, Nemeroff C (eds) Neuropsychopharmacology: the fifth generation of progress. American College of Neuropsychopharmacology, pp 132–45
Mattson MP (2008) Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci 1144:97–112
May MJ, Li L, Hayslett K, Qu Z (2006) Ascorbate transport and recycling by SH-SY5Y neuroblastoma cells: response to glutamate toxicity. Neurochem Res 31:785–794
Moonen G, Rogister B, Leprince P, Rigo JM, Delree P, Lefebvre PP, Schoenen J (1990) Neurono-glial interactions and neural plasticity. Progr Brain Res 86: 63–73 (Quoted by Baydas et al. (2006))
Nakanishi Y, Fujimoto KM, Salunga TL, Nomoto K, Nakano M, Selmi C, Gershwin M (2008) Monosodium glutamate (MSG): a villain and promoter of liver inflammation and dysplasia. J Autoimmun 30:242–250
Padayatty SJ, Katz A, Wang Y, Eck P, Christopher CC, Dutta A, Dutta SK, Levine M (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35
Pavlovic V, Sarac M (2010) The role of ascorbic acid and monosodium glutamate in thymocyte apoptosis. Bratisl Lek listy 111:357–360
Pekny M, Pekna M (2004) Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol 204:428–437
Pekny M, Eliasson C, Siushansian R, Ding M, Dixon SJ et al (1999) The impact of genetic removal of gfap and/or vimentin on glutamine levels and transport of glucose and ascorbate in astrocytes. Neurochem Res 24:1357–1362
Rascher K (1981) Monosodium glutamate-induced lesions in the rat cingulate cortex. Cell Tissue Res 220:239–250
Re DB, Boucraut J, Samuel D, Birman S, Goff KL, Had-Aissouni L (2003) Glutamate transport alteration triggers differentiation-state selective oxidative death of cultured astrocytes: a mechanism different from excitotoxicity depending on intracellular GSH contents. J Neurochem 85:1159–1170
Reistad T, Mariussen E, Ring A, Fonnum F (2007) In vitro toxicity of tetrabromobisphenol-a on cerebellar granule cells: cell death, free radical formation, calcium influx and extracellular glutamate. Toxicol Sci 96:268–278
Reiter RJ (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533
Schubert D, Piasecki D (2001) Oxidative glutamate toxicity can be a component of the excitotoxicity cascade. J Neurosci 21:7455–7462
Sharma P (1996) Effect of ascorbic acid on hyperoxic rat astrocytes. Neurosci 72:391–397
Shih AY, Erb H, Sun X, Toda S, Kalivas PW, Murphy TH (2006) Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci 26:10514–10523
Spence RD, Zhen Y, White S, Schlinger BA, Lainy B (2009) Recovery of motor and cognitive function after cerebellar lesions in a songbird—role of estrogens. Eur J Neurosci 29:1225–1234
Sriram K, Benkovic SA, Hebert MA, Miller DB, O’Callaghan JP (2004) Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1, 2, 3, 6 tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? J Biol Chem; 279:19936–19947
Stafstrom CE (2004) The role of glutamate transporters in developmental epilepsy: a concept in flux. Epilepsy Curr 4:243–244
Standring S, Ellis H, Healy JC, Johnson D, Williams A (2005) Gray’s anatomy. Elsevier Churchill Livingstone, New York
Steiner J, Bernstein HG, Bielau H, Berndt A, Brisch R, Mawrin C, Keilhoff G, Bogerts B (2007) Evidence for a wide extra-astrocytic distribution of S100B in human brain. BMC Neurosci 8:2–12
Suárez I, Bodega G, Rubio M, Fernández B (1992) Sexual dimorphism in the hamster cerebellum demonstrated by glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity. Glia 5:10–16
Szydlowska K, Zawadzka M, Kaminska B (2006) Neuroprotectant FK506 inhibits glutamate-induced apoptosis of astrocytes in vitro and in vivo. J Neurochem 99:965–975
Takuma K, Matsuda T, Hashimoto H, Kitanaka J, Asano S, Kishida Y, Baba A (1996) Role of Na1-Ca21 exchanger in agonist-induced Ca21 signaling in cultured rat astrocytes. J Neurochem 67:1840–1845
Tojo A, Onozato ML, Kobayashi N, Goto A, Matsuoka H, Fujita T (2002) Angiotensin II and oxidative stress in Dahl salt-sensitive rat with heart failure. Hypertension 40:834–839
Tsao CS, Leung PY, Young M (1987) Effect of dietary ascorbic acid intake on tissue vitamin C in mice. J Nutr 117:291–297
Vinodini N, Nayanatara AK, Gowda KM, Ahamed B, Ramaswamy C, Bhat RM (2008) Effect of monosodium glutamate-induced oxidative damage on rat testis. J Chin Clin Med 3:370–373
Walker R, Lupien JR (2000) The safety evaluation of monosodium glutamate. J Nutr 130:1049S–1052S
Ye ZC, Sontheimer H (1998) Astrocytes protect neurons from neurotoxic injury by serum glutamate. Glia 22:237–248
Zai H, Kusano M, Hosaka H, Shimoyama Y, Nagoshi A, Maeda M, Mori KO (2009) Monosodium L-glutamate added to a high-energy, high-protein liquid diet promotes gastric emptying. Am J Clin Nutr 89:431–435
Acknowledgments
We would like to extend our thanks and appreciation to The Deanship of Scientific Reasearch, Taibah University, KSA for supporting this project by grant No. 431/693. Special thanks also to Prof. Khaled Hamed Almesalamy for his direction, assistance, and guidance without his knowledge and assistance this study would not have been successful. Also, we would like to appreciate efforts of Prof. Amira Ibrahim Alboraei for revision of this work.
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Hashem, H.E., El-Din Safwat, M.D. & Algaidi, S. The effect of monosodium glutamate on the cerebellar cortex of male albino rats and the protective role of vitamin C (histological and immunohistochemical study). J Mol Hist 43, 179–186 (2012). https://doi.org/10.1007/s10735-011-9380-0
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DOI: https://doi.org/10.1007/s10735-011-9380-0