Evaluation of Biochemical, Hematological and Histological Parameters in Non Diabetic and Diabetic Wistar Rats Fed with Monosodium Glutamate

Hellen D. B. Maluly, Miguel A. Areas, Primavera Borelli, Felix G. R. Reyes

Department of Food Science, School of Food Engineering, University of Campinas, S?o Paulo, Brazil.
Department of Structural and Functional Biology, Institute of Biology, University of Campinas, S?o Paulo, Brazil.
Faculty of Pharmaceutical Sciences, University of S?o Paulo, S?o Paulo, Brazil..

DOI: 10.4236/fns.2013.41010                

Abstract

The parenteral or oral administration of monosodium glutamate (MSG) has been reported to have a deleterious effect on the hypothalamic arcuate nucleus, which changes appetite control. This alteration in function may lead to obesity and disorders related to metabolic syndrome, such as alterations in carbohydrate metabolism (glucose and insulin resistance), dyslipidemia and cardiovascular disease. This study evaluates the induction of metabolic alterations due to subchronic consumption of diets containing MSG at levels of 1.0%, 2.5% and 5.0%. Initially the animals (newborn male Wistar rats) consumed the diets containing MSG for a period of 70 days. At the end of this period diabetes was induced by streptozotocin (STZ) and the rats maintained on the same diets for additional 21 days. The induction of diabetes is based on the susceptibility of diabetic animals to metabolic disorders. Methods capable of evaluating the entire metabolic profile of the diabetic condition were used, including biochemical tests and tests able to detect alterations in the organs usually affected by this disease. It was concluded that the consumption of diets containing up to 5.0% MSG did not change the studied parameters for both: diabetic or non-diabetic animals. The alterations observed in the diabetic animals mainly reflected metabolic changes caused by the disease and were not related to the administration of MSG.

Keywords

MSG; Glutamate; Wistar Rat; Diabetes

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. Jinap and P. Hajeb, “Glutamate. Its Applications in Food and Contribution to Health,” Appetite, Vol. 55, No. 1, 2010, pp. 1-10. doi:10.1016/j.appet.2010.05.002
[2]	S. Yamaguchi and K. Ninomiya, “Umami and Food Palatability,” The Journal of Nutrition, Vol. 130, Suppl. 4, 2000, pp. 921-926.
[3]	Toxicological Evaluation of Certain Food Additives, “L-Glutamic Acid and Its Ammonium, Calcium, Monosodium and Potassium Salts,” WHO Food Additives Series, No. 22, Cambridge University Press, Cambridge, 1988, pp. 97-161.
[4]	US Food and Drug Administration, “Database of GRAS Substances that Were Evaluated by the Select Committee on GRAS Substances (SCOGS),” 2006. http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASSubstancesSCOGS Database/default.htm
[5]	FASEB, “Analysis of Adverse Reactions to Monosodium Glutamate (MSG), Report,” Life Sciences Research Office, Federation of American Societies of Experimental Biology, Washington DC, 1995.
[6]	Y. S. Diniz, A. A. H. Fernandes, K. E. Campos, F. Mani, B. O. Ribas and E. L. B. Novelli, “Toxicity of Hypercaloric Diet and Monosodium Glutamate: Oxidative Stress and Metabolic Shifting in Hepatic Tissue,” Food and Chemical Toxicology, Vol. 42, No. 2, 2004, pp. 313-319. doi:10.1016/j.fct.2003.09.006
[7]	C. Broberger, “Brain Regulation of Food Intake and Appetite: Molecules and Networks,” Journal of Internal Medicine, Vol. 258, No. 4, 2005, pp. 301-327. doi:10.1111/j.1365-2796.2005.01553.x
[8]	M. Hermanussen and J. A. F. Tresguerres, “Does High Glutamate Intake Cause Obesity?” Journal of Pediatric Endocrinology and Metabolism, Vol. 16, 2003, pp. 965-968. doi:10.1515/JPEM.2003.16.7.965
[9]	M. Hermanussen, A. P. García, M. Sunder, M. Voigt, V. Salazar and J. A. F. Tresguerres, “Obesity, Voracity, and Short Stature: The Impact of Glutamate on the Regulation of Appetite”, European Journal of Clinical Nutrition, Vol. 60, 2006, pp. 25-31. doi:10.1038/sj.ejcn.1602263
[10]	M. A. Rol de Lama, A. Perez Romero, C. Ariznavarreta, M. Hermanunssen and J. A. F. Tresguerres, “Periodic Growth in Rats,” Annals of Human Biology, Vol. 25, No. 5, 1998, pp. 441-451. doi:10.1080/03014469800006682
[11]	M. W. Schwartz, S. C. Woods, D. Porte Jr., R. J. Seeley and D. G. Baskin, “Central Nervous System Control of Food Intake,” Nature, Vol. 404, 2000, pp. 661-671.
[12]	K. He, L. Zhao, M. L. Daviglus, A. R. Dyer, L. Van Horn, D. Garside, L. Zhu, D. Guo, Y. Wu, B. Zhou and J. Stamler, “Association of Monosodium Glutamate Intake with Overweight in Chinese Adults: The INTERMAP Study,” Obesity, Vol. 16, No. 8, 2008, pp. 1875-1880. doi:10.1038/oby.2008.274
[13]	Z. Shi, N. D. Luscombe-Marsh, G. A. Wittert, B. Yuan, Y. Dai, X. Pan and A. W. Taylor, “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,” British Journal of Nutrition, Vol. 7, 2010, pp. 1-7.
[14]	J. I. Elliott, H. Ewchand and D. M. Altmann, “Streptozotocin-Induced Diabetes in Mice Laking Alphabeta T Cells,” Clinical and Experimental Immunology, Vol. 109, No. 1, 1997, pp. 116-120. doi:10.1046/j.1365-2249.1997.4241319.x
[15]	J. A. White, R. J. Hart and J. C.Fry, “An Evaluation of the Waters Pico-Tag System for the Amino-Acid-Analysis of Food Materials,” The Journal Automatic Chemistry, Vol. 8, No. 4, 1986, pp. 170-177. doi:10.1155/S1463924686000330
[16]	S. R. Hagen, B. Frost and J. Augustin, “Precolumn Phenylisothiocyanate Derivatization and Liquid Chromatography of Amino Acids in Food,” Journal Association of Official Analytical Chemistry, Vol. 72, No. 6, 1989, pp. 912-916.
[17]	S. A. Cohen, B. A. Bidlingmeyer and T. L. Tarvin, “PITC Derivatives in Amino Acid Analysis,” Nature, Vol. 320, No. 6064, 1986, pp. 769-770. doi:10.1038/320769a0
[18]	M. M. Bradfordm, “A Rapid and Sensitive Method for Quantification of Microgram Quantities of Protein Utilizing The Principle of Protein-Dye-Binding,” Analytical Biochemistry, Vol. 72, No. 1-2, 1976, pp. 248-254. doi:10.1016/0003-2697(76)90527-3
[19]	J. Schaffer, O. Gallay and R. Ladenstein, “Glutathione Transferase from Bovine Placenta. Preparation, Biochemical Characterization, Crystallization, and Preliminary Crystallographic Analysis of a Neutral Class PI Enzyme,” The Journal of Biological Chemistry, Vol. 263, No. 33, 1988, pp. 17405-17411.
[20]	G. Cohen, D. Dembiec and J. Marcus, “Measurement of Catalase Activity in Tissue Extracts,” Analytical Biochemistry, Vol. 34, No. 1, 1970, pp. 30-38. doi:10.1016/0003-2697(70)90083-7
[21]	B. Tang, Y. Wang and Z. Z. Chen, “Catalytic Spectrofluorimetric Determination of Superoxide Anion Radical and Superoxide Dismutase Activity Using N,N-Dimethylaniline as the Substrate for Horseradish Peroxidase (HRP),” Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscope, Vol. 58, No. 12, 2002, pp. 2557-2562. doi:10.1016/S1386-1425(02)00007-0
[22]	T. Kondoh and K. Torii, “MSG Intake Suppresses Weight Gain, Fat Deposition, and Plasma Leptin Levels in Male Sprague-Dawley Rats,” Physiology & Behavior, Vol. 95, No. 1-2, 2008, pp. 135-144. doi:10.1016/j.physbeh.2008.05.010
[23]	L. D. Stegink, L. J. Filer Jr. and G. L. Baker, “Plasma Glutamate Concentrations in Adult Subjects Ingesting Monosodium L-Glutamate in Consommé,” The American Journal of Clinical Nutrition, Vol. 42, No. 2, 1985, pp. 220-225.
[24]	L. D. Stegink, L. J. Filer Jr. and G. L. Baker, “Plasma Amino Acid Concentrations in Normal Adults Ingesting Aspartame and Monosodium L-Glutamate as Part of a Soup/Beverage Meal,” Metabolism, Vol. 36, No. 11, 1987, pp. 1073-1079. doi:10.1016/0026-0495(87)90028-X
[25]	P. J. Tsai and P. C. Huang, “Circadian Variations in Plasma and Erythrocyte Glutamate Concentrations in Adult Men Consuming a Diet with and without Added Monosodium Glutamate,” The Journal of Nutrition, Vol. 130, No. 4, 2000, pp. 1002-10044.
[26]	P. J. Reeds, D. G. Burrin and F. Jahoor, “Enteral Glutamate Is Almost Completely Metabolized in First Pass by the Gastrointestinal Tract of Infant Pigs,” The American Journal of Physiology, Vol. 1270, No. 3, 1996, pp. 413-418.
[27]	D. G. Burrin and B. Stoll, “Metabolic Fate and Function of Dietary Glutamate in the Gut,” The American Journal of Clinical Nutrition, Vol. 90, No. 3, 2009, pp. 850-856. doi:10.3945/ajcn.2009.27462Y
[28]	O. R. Simon and M. E. West, “Unstable Diabetic State Produced by Small Dose Streptozotocin in Rats,” The West Indian Medical Journal, Vol. 42, No. 4, 1992, pp. 146-149.
[29]	K. S. Collison, Z. Maqbool, S. M. Saleh, A. Inglis, N. J. Makhoul, R. Bakheet, M. Al-Johi, R. Al-Rabiah, M. Z. Zaidi and F. A. Al-Mohanna, “Effect of Dietary Monosodium Glutamate on Trans Fat-Induced Nonalcoholic Fatty Liver Disease,” Journal of Lipid Research, Vol. 50, No. 8, 2008, pp. 1521-1537. doi:10.1194/jlr.M800418-JLR200
[30]	G. Marchesini, E. Bugianesi, G. Forlani, F. Cerrelli, M. Lenzi, R. Manini, S. Natale, E. Vanni, N. Villanova, N. Melchionda and M. Rizzetto, “Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome,” Hepatolology, Vol. 37, No 4, 2003, pp. 917-923. doi:10.1053/jhep.2003.50161
[31]	G. Ozansoy, B. Akin, F. Aktan and C. Karasu, “Short-Term Gemfibrozil Treatment Reverses Lipid Profile and Peroxidation but Does Not Alter Blood Glucose and Tissue Antioxidant Enzymes in Chronically Diabetic Rats,” Molecular and Cellular Biochemistry, Vol. 216, No. 1-2, 2001, pp. 59-63. doi:10.1023/A:1011000327529
[32]	U. Bayraktutan, “Free Radicals, Diabetes and Endothelial Dysfunction,” Diabetes, Obesity and Metababolism, Vol. 4, No. 4, 2002, pp. 224-238. doi:10.1046/j.1463-1326.2002.00184.x
[33]	K. Singh and P. Ahluwalia, “Studies on the Effect of Monosodium Glutamate [MSG] Administration on Some Antioxidant Enzymes in the Arterial Tissue of Adult Male Mice,” Journal of Nutrition Science and Vitaminololy (Tokyo), Vol. 49, No. 2, 2003, pp. 145-148. doi:10.3177/jnsv.49.145
[34]	E. O. Farombi and O. O. Onyema, “Monosodium Glutamate-Induced Oxidative Damage and Genotoxicity in the Rat: Modulatory Role of Vitamin C, Vitamin E and Quercetin,” Human & Experimental Toxicology, Vol. 25, No. 5, 2006, pp. 251-259. doi:10.1191/0960327106ht621oa
[35]	S. K. Jain, “Hyperglycemia Can Cause Membrane Lipid Peroxidation and Osmotic Fragility in Human Red Blood Cells,” The Journal of Biological Chemistry, Vol. 264, No. 35, 1989, pp. 21340-21345.
[36]	K. G. Alberti and P. Z. Zimmet, “Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications. Part 1: Diagnosis and Classification of Diabetes Mellitus Provisional Report of a WHO Consultation,” Diabetic Medicine, Vol. 15, No. 7, 1998, pp. 539-553. doi:10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S
[37]	K. C. Tan, I. R. Mackay, P. Z. Zimmet, B. R. Hawkins and K. S. Lam, “Metabolic and Immunologic Features of Chinese Patients with Atypical Diabetes Mellitus,” Diabetes Care, Vol. 23, No. 3, 2000, pp. 335-338. doi:10.2337/diacare.23.3.335