MEASUREMENT OF DNA DAMAGE, OXIDATIVE STRESS, AND GENE EXPRESSION OF β-CATENIN AND P53 GENES IN LIVER AND BRAIN OF MALE MICE RECEIVING MONOSODIUM L-GLUTAMATE MONOHYDRATE
Keywords:Monosodium L-glutamate monohydrate, Oxidative stress, DNA damage, DNA fragmentation, Quantitative polymerase chain reaction, Mice
Introduction: Monosodium L-glutamate (MSG) monohydrate is a widespread nutritional additive and flavoring agent frequently consumed all over the world. In this study, we investigate the action of daily oral intake of MSG monohydrate in vivo using mammalian systems.
Methods: Mice divided as follows: Group I (normal control), Group II, and Group III treated with MSG for 2 and 4 weeks, respectively. Brain and liver dissected out for the detection of fragmented DNA, DNA damage, and assay of oxidative stress markers. Moreover, expression levels of ß-Cat and p53 genes were measured by a real-time quantitative polymerase chain reaction.
Results: The results showed a significant difference in MSG-treated group at the 2-time intervals than the control one regarding parameters of oxidative stress, and these were accompanied by a significant decline in glutathione (GSH) and a ratio of oxidized and reduced GSH in both tissues. Significant elevation of laddered DNA and oxidative DNA damage was observed in groups treated with MSG. In addition, a significant decline in gene expression of ß-Catenin in liver and brain tissues with elevations in the gene expression of p53 in the brain. Furthermore, the p53 gene in liver tissue was significantly upregulated in mice administered MSG for 15 days and was downregulated after 30 days of MSG intake compared with the control.
Conclusion: According to our results, oral consumption of MSG leads to oxidative stress-mediated DNA damage and apoptosis.
Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, et al. Review of alleged reaction to monosodium glutamate and outcome of a multicenter double-blind placebo-controlled study. J Nutr 2000;130:1058S-62.
OnyemaOO, Farombi EO, Emerole GO, Ukoha AI, Onyeze GO. Effect of Vitamin E on monosodium glutamate induced hepatotoxicity and oxidative stress in rats. Indian J Biochem Biophys 2006;43:20-4.
BojanićV, Bojanić Z, Najman S, Savić T, Jakovljević V, Najman S, et al. Diltiazem prevention of toxic effects of monosodium glutamate on ovaries in rats. Gen Physiol Biophys 2009;28:149-54.
Abass MA, El-Haleem MR. Evaluation of monosodium glutamate induced neurotoxicity and nephrotoxicity in adult male albino rats. J Am Sci 2011;7:264-70.
Ebaid H, Tag H. Monosodium glutamate toxic effect on spleen structure and potentiality of recovery in adult albino rats. Egypt Acad J Biol Sci B Zool 2012;4:1-8.
Khatab HA, Elhaddad NS, Chiang CJ. ???. Br Biotechnol J 2015;8:1-11.
Abuzaid AS, Iskandar EY, Kurniati NF, Adnyana IK. Preventive effect on obesity of mangosteen (Garcinia mangostana L.) pericarp ethanolic extract by reduction of fatty acid synthase level in monosodium glutamate and high-calorie diet-induced male Wistar rats. Asian J Pharm Clin Res 2016;9:3-6.
Tawfik MS, Al-Badr N. Adverse effects of monosodium glutamate on liver and kidney functions in adult rats and potential protective effect of Vitamins C and E. Food Nutr Sci 2012;3:651-9.
Ortiz GG, Bitzer-Quintero OK, Zárate CB, Rodríguez-Reynoso S, Larios-Arceo F, Velázquez-Brizuela IE, et al. Monosodium glutamate-induced damage in liver and kidney: A morphological and biochemical approach. Biomed Pharmacother 2006;60:86-91.
Pavlović V, Cekić S, Kocić G, Sokolović D, Zivković V. Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat thymocyte culture. Physiol Res 2007;56:619-26.
Appaiah KM. Monosodium glutamate in foods and its biological effects. Ensuring Glob Food Saf 2010; ???:217-26.
Plaitakis A, Shashidharan P. Glutamate transport and metabolism in dopaminergic neurons of substantia nigra: Implications for the pathogenesis of Parkinson’s disease. J Neurol 2000;247:II25-35.
Sriram BS, Ravichandra V. An experimental study evaluating the influence of quercetin on monosodium glutamate-induced depression in swiss albino male mice. Asian J Pharm Clin Res 2019;12:292-4.
Lau A, Tymianski M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflügers Arch Eur J Physiol 2010;460:525-42.
Adeyemo OA, Farinmade AE. Genotoxic and cytotoxic effects of food flavor enhancer, monosodium glutamate (MSG) using Allium cepa assay. Afr J Biotechnol 2013;12:1459-66.
Ataseven N, Yüzbaşioğlu D, Keskin AÇ, Ünal F. Genotoxicity of monosodium glutamate. Food Chem Toxicol 2016;91:8-18.
Hashem HE, El-Din Safwat MD, 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 Histol 2012;43:179-86.
Khalaf HA, Arafat EA. Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: A histological study. Int J Clin Exp Pathol 2015;8:15498-510.
Karatepe M. Simultaneous determination of ascorbic acid and free malondialdehyde in human serum by HPLC-UV. LCGC Asia Pac 2004;7:7-9.
Jayatilleke E, Shaw S. A high-performance liquid chromatographic assay for reduced and oxidized glutathione in biological samples. Anal Biochem 1993;214:452-7.
Papadoyannis IN, Samanidou VF, Nitsos CC. Simultaneous determination of nitrite and nitrate in drinking water and human serum by high performance anion-exchange chromatography and Uv detection. J Liq Chromatogr Relat Technol 1999;22:2023-41.
Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, et al. Single cell gel/comet assay: Guidelines for in vitro and in vivo genetic toxicology testing. Environ Mol Mutagen 2000;35:206-21.
Olive PL, Banáth JP. Multicell spheroid response to drugs predicted with the comet assay. Cancer Res 1997;57:5528-33.
Sriram MI, Kanth SB, Kalishwaralal K, Gurunathan S. Antitumor activity of silver nanoparticles in Dalton’s lymphoma ascites tumor model. Int J Nanomed 2010;5:753-62.
Gutierrez MI, Bhatia K, Siwarski D, Wolff L, Magrath IT, Mushinski JF, et al. Infrequent p53 mutation in mouse tumors with deregulated myc. Cancer Res 1992;52:1032-5.
Shimada I, Takahashi H, Nakanishi T, Kami K, Arata Y. A novel NMR method for determining the interfaces of large protein-protein complexes. Nat Struct Biol 2000;7:220-3.
Oh SW, Harris JA, Ng L, Winslow B, Cain N, Mihalas S, et al. A mesoscale connectome of the mouse brain. Nature 2014;508:207-14.
Bhattacharya T, Bhakta A, Ghosh SK. Long term effect of monosodium glutamate in liver of albino mice after neo-natal exposure. Nepal Med Coll J 2011;13:11-6.
Husarova V, Ostatnikova D. Monosodium glutamate toxic effects and their implications for human intake: A review. JMED Res 2013;2013:1-12.
Umukoro S, Oluwole GO, Olamijowon HE, Omogbiya AI, Eduviere AT. Effect of monosodium glutamate on behavioral phenotypes, biomarkers of oxidative stress in brain tissues and liver enzymes in mice. Artic World J Neurosci 2015;5:339-49.
Pavlovic V, Pavlovic D, Kocic G, Sokolovic D, Jevtovic-Stoimenov T, Cekic S, et al. Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus. Mol Cell Biochem 2007;303:1610-6.
Diniz YS, Fernandes AA, Campos KE, Mani F, Ribas BO, Novelli EL. Toxicity of hypercaloric diet and monosodium glutamate: Oxidative stress and metabolic shifting in hepatic tissue. Food Chem Toxicol 2004;42:313-9.
Onaolapo OJ, Aremu OS, Onaolapo AY. Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice. Naunyn Schmiedebergs Arch Pharmacol 2017;390:677-89.
Thomas M, George S. Effect of Piper longum Linn, in monosodium glutamate toxicity in rats. Indian J Anim Sci 2010;80:857-63.
Farombi O, Onyema OO, Farombi E. Monosodium glutamate-induced oxidative damage and genotoxicity in the rat: Modulatory role of Vitamin C, Vitamin E and quercetin. Hum Exp Toxicol 2006;25:251-9.
Eweka AO, Igbigbi PS, Ucheya RE. Histochemical studies of the effects of monosodium glutamate on the liver of adult Wistar rats. Ann Med Health Sci Res 2011;1:21-30.
Abdel-Aziem SH, Abd El-Kader HA, Ibrahim FM, Sharaf HA, El Makawy AI. Evaluation of the alleviative role of Chlorella vulgaris and Spirulina platensis extract against ovarian dysfunctions induced by monosodium glutamate in mice. J Genet Eng Biotechnol 2018;16:653-60.
Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A. Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiol Rev 2009;89:27-71.
Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: Implications for neuroimaging. Trends Neurosci 2004;27:489-95.
Murphy BF, Saunders JR, O’Bryan MK, Kirszbaum L, Walker ID, D’Apice AJ. SP-40,40 is an inhibitor of C5b-6-initiated haemolysis. Int Immunol 1989;1:551-4.
Zündorf G, Kahlert S, Bunik VI, Reiser G. α-Ketoglutarate dehydrogenase contributes to production of reactive oxygen species in glutamate-stimulated hippocampal neurons in situ. Neuroscience 2009;158:610-6.
Ashcroft M, Vousden KH. Regulation of p53 stability. Oncogene 1999;18:7637-43.
Ashcroft M, Taya Y, Vousden KH. Stress signals utilize multiple pathways to stabilize p53. Mol Cell Biol 2000;20:3224-33.
Sadot E, Geiger B, Oren M, Ben-Ze’ev A. Down-regulation of beta-catenin by activated p53. Mol Cell Biol 2001;21:6768-81.
Charni M, Aloni-Grinstein R, Molchadsky A, Rotter V. p53 on the crossroad between regeneration and cancer. Cell Death Differ 2017;24:8-14.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.