Monosodium glutamate below the neurotoxic doses has no cytotoxic effect on mouse mesenchymal stem cells
Abstract
Objective: Monosodium glutamate appear as a food additive that listed in the group of flavor enhancers is
continuously used in various types of foods. Monosodium glutamate is the sodium
salt of glutamic acid, one of the most abundant naturally-occurring
non-essential amino acids. U.S. Food and Drug Administration reported that
monosodium glutamate is safe for use in food. However, the excessive use of
monosodium glutamate causes dizziness, nausea and vomiting. Due to reports, it
causes obesity. In this study it was aimed to find out the cytotoxicity of
monosodium glutamate and the role on the selected genes, which have role on
obesity.
Method: In our
study, mice were used which are known to be the most sensitive in terms of
toxicity. The cytotoxic effects of monosodium glutamate on mouse mesenchymal
stem cells at monosodium glutamate doses below the blood dose (100-130 µmol/dl)
that reported as the neuronal damage threshold in mice were studied. Furthermore leptin-lep
and ghrelin / obestatin in
prepropeptide-GHRL gene expressions in order to find out the role of
monosodium glutamate in obesity were analyzed.
Results: Monosodium
glutamate below the toxic dose does not have a cytotoxic effect on mouse
mesenchymal stem cells. Also no
expression change in applied monosodium glutamate doses was observed in genes
which are known to be associated with obesity.
Conclusions: Our results support that monosodium glutamate has no toxic effect on
stem cells in uses in certain doses.
Keywords
Monosodium glutamate mouse mesenchymal stem cells leptin gene ghrelin/obestatin prepropeptide gene
References
- 1. Yamaguchi S. Basic properties of umami and effects on humans. Physiology & Behavior 1991; 49: 833-41.
- 2. Kurihara K. Glutamate: from discovery as a food flavor to role as a basic taste (umami)? The American Journal of Clinical Nutrition 2009; 90: 719-22.
- 3. Tarasoff L, Kelly MF. Monosodium L-glutamate: a double-blind study and review. Food Chem. Toxicol 1993; 31: 1019-35.
- 4. Yamaguchi S. Basic properties of umami and effects on humans. Physiology & Behavior 1991; 49: 833-41.
- 5. Shi Z, Luscombe-Marsh ND, Wittert GA, Yuan B, Dai Y, Pan X, Taylor AW. Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: Findings from the Jiangsu Nutrition Study of Chinese adults. Br J Nutrition 2010; 104: 457-63.
- 6. Jin YJ, Cao PJ, Bian WH, Li ME, Zhou R, Zhang LY, Yang MZ. BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity. Nutr Neurosci 2015; 18: 376-82.
- 7. 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.
- 8. Walker R. The significance of excursions above the ADI. Case study: monosodium glutamate. Regul Toxicol Pharmacol 1999; 30(2 Pt 2): 119-21.
- 9. Brennan AM, Mantzoros CS. Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications. Nat Clin Pract Endocrinol Metab 2006; 2: 318-27.
- 10. Pan H, Guo J, Su Z. Advances in understanding the interrelations between leptin resistance and obesity. Physiology & Behavior 2014; 130: 157-69.
- 11. Zhang L, Peng LP, Wu N, Li LP. Development of bone marrow mesenchymal stem cell culture in vitro. Chin Med J (Engl) 2012; 125: 1650-5.
- 12. Williams AR, Hare MJ, Dimmeler S, Losordo D. Mesenchymal Stem Cells, Biology, Pathophysiology, Translational Findings, and Therapeutic Implications for Cardiac Disease. Circulation Research. 2011; 109: 923-40.
- 13. Alkahtani A, Alkahtany SM, Anil S. An in vitro Evaluation of the Cytotoxicity of Varying Concentrations of Sodium Hypochlorite on Human Mesenchymal Stem Cells. J Contemporary Dental Practice 2014; 15: 473-81.
- 14. Jeonga JY, Suresha S, Park MN, Jang M, Park S, Gobianand K, You S, Yeon SH, Lee HJ. Effects of Capsaicin on Adipogenic Differentiation in Bovine Bone Marrow Mesenchymal Stem Cell. Asian-Australasian J Animal Sci 2014; 27: 1783-93.
- 15. Ottaway N, Mahbod P, Rivero B, Norman LA, Gertler A, D'Alessio DA, Perez-Tilve D. Diet-induced obese mice retain endogenous leptin action. Cell Metab 2015; 21: 877-82.
- 16. Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol 2017; 13: 338-51.
- 17. Bali A, Jaggi AS. An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and Depression. Curr Drug Targets 2016; 17: 495-507.
- 18. Çoban ZD, Güzel H, Demircan A, Arslan M, Demirhan FS, Karaağaç N, Babayiğit N, Öveç M, Sönmez E, Kaynak M, Bal R, Yurdakul M, Satman M, Ada MF, Akyüz TZ, Ceylan MM, Daştan A, Farhmand N, Güran Ş. Mesenchymal stem cells obtained from mouse represents high viability and steamness properties in the early phase of cell culture. Gülhane Medical Journal (in press).
- 19. Lennon DP, Caplan AI. Isolation of human marrow-derived mesenchymal stem cells. Exp Hematol 2006; 34: 1604-05.
- 20. Coco-Martin JM, Oberink JW, van der Velden-de Groot TA, Beuvery EC. Viability measurements of hybridoma cells in suspension cultures. Cytotechnology 1992; 8: 57-64.
- 21. Çoban ZD, Avcu F, Ural AU, Kuzhan O, Güran Ş. The sitotoxic effect of gemcitabine on multiple myeloma (RPMI-8226) and Ig G plasma cell leukemia (ARH 77) cell lines Gulhane Medical Journal 2012; 54: 263-6.
- 22. Salque M, Bogucki PI, Pyzel P, Sobkowiak-Tabaka I, Grygiel R, Szmyt M, Evershed RP. Earliest evidence for cheese making in the sixth millennium bc in northern Europe. Nature 2013; 493: 522-5.
- 23. Ikeda K. New seasonings. Chem Senses 2002; 27: 847-9.
- 24. Tarasoff L, Kelly MF. Monosodium L-glutamate: a double-blind study and review. Food Chem Toxicol 1993; 31: 1019-35.
- 25. Pelantová H, Bártová S, Anýž J, et al. Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity. Anal Bioanal Chem 2016; 408: 567-78.
- 26. Çetin Kardeşler A, Başkale E. Investigation of the behavioral and neurochemical effects of monosodium glutamate on neonatal rats. Turk J Med Sci 2017 12; 47:1002-11.
- 27. Contini MDC, Fabro A, Millen N, Benmelej A, Mahieu S. Adverse effects in kidney function, antioxidant systems and histopathology in rats receiving monosodium glutamate diet. Exp Toxicol Pathol 2017 May 15. pii: S0940-2993(16)30333-5. doi: 10.1016/j.etp.2017.03.003.
- 28. Aragonès G, Ardid-Ruiz A, Ibars M, Suárez M, Bladé C. Modulation of leptin resistance by food compounds. Mol Nutr Food Res 2016 Feb 4. doi: 10.1002/mnfr.201500964.
- 29. Hopkins BD, Goncalves MD, Cantley LC. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol. 2016; 34: 4277-83.
- 30. Zigman JM, Bouret SG, Andrews ZB. Obesity Impairs the Action of the Neuroendocrine Ghrelin System. Trends Endocrinol Metab 2016; 27: 54-63.
- 31. Amitani M, Amitani H, Cheng KC, Kairupan TS, Sameshima N, Shimoshikiryo I, Mizuma K, Rokot NT, Nerome Y, Owaki T, Asakawa A, Inui A. The Role of Ghrelin and Ghrelin Signaling in Aging. Int J Mol Sci 2017 12; 18. pii: E1511. doi: 10.3390/ijms18071511.
Nörotoksik dozun altındaki monosodyum glutamatın fare mezenkimal kök hücreler üzerinde sitotoksik etkisi yoktur
Abstract
Amaç: Monosodyum glutamat lezzet
arttırıcılar grubunda gıda katkı maddesi olarak çeşitli yiyeceklerde
kullanılmaktadır. Monosodyum glutamat glutamik asidin sodyum tuzudur ve doğal
yollarla en fazla oluşan esansiyel olmayan aminoasitlerden biridir. Amerikan Gıda Ve İlaç Teşkilatı (U.S. Food and Drug
Administration) monosodyum glutamatın gıdada kullanımının güvenli olduğunu bildirmiştir.
Ancak aşırı kullanımında baş dönmesi, bulantı kusma yapmaktadır. Makalelerde
obeziteye neden olduğu bildirilmektedir.
Bu çalışmada, monosodyum glutamatın sitotoksik ve obezitede rolü olan
seçilmiş bazı genlere olan etkilerinin bulunması amaçlanmıştır.
Yöntem: Çalışmamıza toksisite
yönünden en hassas organizma olduğu bilinen fareler alınmıştır. Monosodyum
glutamatın fare mezenkimal hücreler üzerine olan sitotoksik etkisi farelerde
nöronal hasar oluşturduğu bildirilen kan dozunun (100-130 µmol/dl) altındaki
dozlar kullanılarak çalışılmıştır. Ayrıca monosodyum glutamatın obezite üzerine
olan etkisini bulmak için “leptin-lep”
ve “Ghrelin/Obestatin Prepropeptide-GHRL”
genlerine ait ekspresyon değişikliklerine bakılmıştır.
Bulgular:
Monosodyum glutamatın toksik dozun altında fare mezenkimal kök
hücre üzerinde bir sitotoksik etkisi olmadığı bulunmuştur. Uygulanan monosodyum
glulatamat dozlarında hücrede obezite ile ilgili olduğu bilinen genlerin
ekspresyonlarını değiştirmediği saptanmıştır.
Sonuç: Sonuçlarımız
monosodyum glutamatın gıdada belli dozlarda kullanımının kök hücreler üzerine
toksik bir etkisi olmadığını destekler niteliktedir.
Keywords
Monosodyum glutamat fare mezenkimal kök hücresi leptin geni ghrelin/obestatin prepropeptide geni
References
- 1. Yamaguchi S. Basic properties of umami and effects on humans. Physiology & Behavior 1991; 49: 833-41.
- 2. Kurihara K. Glutamate: from discovery as a food flavor to role as a basic taste (umami)? The American Journal of Clinical Nutrition 2009; 90: 719-22.
- 3. Tarasoff L, Kelly MF. Monosodium L-glutamate: a double-blind study and review. Food Chem. Toxicol 1993; 31: 1019-35.
- 4. Yamaguchi S. Basic properties of umami and effects on humans. Physiology & Behavior 1991; 49: 833-41.
- 5. Shi Z, Luscombe-Marsh ND, Wittert GA, Yuan B, Dai Y, Pan X, Taylor AW. Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: Findings from the Jiangsu Nutrition Study of Chinese adults. Br J Nutrition 2010; 104: 457-63.
- 6. Jin YJ, Cao PJ, Bian WH, Li ME, Zhou R, Zhang LY, Yang MZ. BDNF levels in adipose tissue and hypothalamus were reduced in mice with MSG-induced obesity. Nutr Neurosci 2015; 18: 376-82.
- 7. 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.
- 8. Walker R. The significance of excursions above the ADI. Case study: monosodium glutamate. Regul Toxicol Pharmacol 1999; 30(2 Pt 2): 119-21.
- 9. Brennan AM, Mantzoros CS. Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications. Nat Clin Pract Endocrinol Metab 2006; 2: 318-27.
- 10. Pan H, Guo J, Su Z. Advances in understanding the interrelations between leptin resistance and obesity. Physiology & Behavior 2014; 130: 157-69.
- 11. Zhang L, Peng LP, Wu N, Li LP. Development of bone marrow mesenchymal stem cell culture in vitro. Chin Med J (Engl) 2012; 125: 1650-5.
- 12. Williams AR, Hare MJ, Dimmeler S, Losordo D. Mesenchymal Stem Cells, Biology, Pathophysiology, Translational Findings, and Therapeutic Implications for Cardiac Disease. Circulation Research. 2011; 109: 923-40.
- 13. Alkahtani A, Alkahtany SM, Anil S. An in vitro Evaluation of the Cytotoxicity of Varying Concentrations of Sodium Hypochlorite on Human Mesenchymal Stem Cells. J Contemporary Dental Practice 2014; 15: 473-81.
- 14. Jeonga JY, Suresha S, Park MN, Jang M, Park S, Gobianand K, You S, Yeon SH, Lee HJ. Effects of Capsaicin on Adipogenic Differentiation in Bovine Bone Marrow Mesenchymal Stem Cell. Asian-Australasian J Animal Sci 2014; 27: 1783-93.
- 15. Ottaway N, Mahbod P, Rivero B, Norman LA, Gertler A, D'Alessio DA, Perez-Tilve D. Diet-induced obese mice retain endogenous leptin action. Cell Metab 2015; 21: 877-82.
- 16. Cui H, López M, Rahmouni K. The cellular and molecular bases of leptin and ghrelin resistance in obesity. Nat Rev Endocrinol 2017; 13: 338-51.
- 17. Bali A, Jaggi AS. An Integrative Review on Role and Mechanisms of Ghrelin in Stress, Anxiety and Depression. Curr Drug Targets 2016; 17: 495-507.
- 18. Çoban ZD, Güzel H, Demircan A, Arslan M, Demirhan FS, Karaağaç N, Babayiğit N, Öveç M, Sönmez E, Kaynak M, Bal R, Yurdakul M, Satman M, Ada MF, Akyüz TZ, Ceylan MM, Daştan A, Farhmand N, Güran Ş. Mesenchymal stem cells obtained from mouse represents high viability and steamness properties in the early phase of cell culture. Gülhane Medical Journal (in press).
- 19. Lennon DP, Caplan AI. Isolation of human marrow-derived mesenchymal stem cells. Exp Hematol 2006; 34: 1604-05.
- 20. Coco-Martin JM, Oberink JW, van der Velden-de Groot TA, Beuvery EC. Viability measurements of hybridoma cells in suspension cultures. Cytotechnology 1992; 8: 57-64.
- 21. Çoban ZD, Avcu F, Ural AU, Kuzhan O, Güran Ş. The sitotoxic effect of gemcitabine on multiple myeloma (RPMI-8226) and Ig G plasma cell leukemia (ARH 77) cell lines Gulhane Medical Journal 2012; 54: 263-6.
- 22. Salque M, Bogucki PI, Pyzel P, Sobkowiak-Tabaka I, Grygiel R, Szmyt M, Evershed RP. Earliest evidence for cheese making in the sixth millennium bc in northern Europe. Nature 2013; 493: 522-5.
- 23. Ikeda K. New seasonings. Chem Senses 2002; 27: 847-9.
- 24. Tarasoff L, Kelly MF. Monosodium L-glutamate: a double-blind study and review. Food Chem Toxicol 1993; 31: 1019-35.
- 25. Pelantová H, Bártová S, Anýž J, et al. Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity. Anal Bioanal Chem 2016; 408: 567-78.
- 26. Çetin Kardeşler A, Başkale E. Investigation of the behavioral and neurochemical effects of monosodium glutamate on neonatal rats. Turk J Med Sci 2017 12; 47:1002-11.
- 27. Contini MDC, Fabro A, Millen N, Benmelej A, Mahieu S. Adverse effects in kidney function, antioxidant systems and histopathology in rats receiving monosodium glutamate diet. Exp Toxicol Pathol 2017 May 15. pii: S0940-2993(16)30333-5. doi: 10.1016/j.etp.2017.03.003.
- 28. Aragonès G, Ardid-Ruiz A, Ibars M, Suárez M, Bladé C. Modulation of leptin resistance by food compounds. Mol Nutr Food Res 2016 Feb 4. doi: 10.1002/mnfr.201500964.
- 29. Hopkins BD, Goncalves MD, Cantley LC. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol. 2016; 34: 4277-83.
- 30. Zigman JM, Bouret SG, Andrews ZB. Obesity Impairs the Action of the Neuroendocrine Ghrelin System. Trends Endocrinol Metab 2016; 27: 54-63.
- 31. Amitani M, Amitani H, Cheng KC, Kairupan TS, Sameshima N, Shimoshikiryo I, Mizuma K, Rokot NT, Nerome Y, Owaki T, Asakawa A, Inui A. The Role of Ghrelin and Ghrelin Signaling in Aging. Int J Mol Sci 2017 12; 18. pii: E1511. doi: 10.3390/ijms18071511.
Details
| Subjects | Health Care Administration |
|---|---|
| Journal Section | Basic Science Research Articles |
| Authors | |
| Publication Date | September 19, 2017 |
| Acceptance Date | July 25, 2017 |
| Published in Issue | Year 2017Volume: 39 Issue: 3 |