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Biological Effect of Sucralose in Diabetic Rats

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DOI: 10.4236/fns.2013.47A010    2,888 Downloads   4,625 Views   Citations

ABSTRACT

Among people that might take a large amount of sucralose, are diabetic people who are attempting to modify their carbohydrate intake. The objective of this study is to evaluate the impact of sucralose; an artificial sweetener derived from sucrose, at a dose approximately twice the ADI on hyperglycemia, hyperlipidemia and oxidative stress in diabetic rats. Diabetes was induced in male albino rats after an intraperitoneal streptozotocin injection (65 mg/kg body weight). Animals with fasting blood glucose levels ≥250 mg/dl were considered diabetics. Sucralose was dissolved in water and administered to rats daily by oral gavages during a period of 6 weeks at a dose of 11 mg/kg body weight. Animals were divided into 4 groups and treated in parallel for 6 weeks. Control: rats received distilled water, Sucralose: rats received sucralose, Diabetic: diabetic rats received distilled water, Diabeticrats + Sucralose: diabetic rats received sucralose. The administration of sucralose to diabetic rats provoked a significant decrease (P < 0.05) of serum glucose and triglyceride levels, a significant increase (P < 0.05) of total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C), while has no effect (P > 0.05) on insulin, compared to their respective values in diabetic rats receiving distilled water. Biochemical analysis in brain and testis tissues showed that sucralose has no effect (P > 0.05) on superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glucose-6-phosphate dehydrogenase (G-6-PDH) activities, and glutathione content (GSH), while reduced thiobarbituric acid reactive substances level (TBARS) (P < 0.05), compared to their respective values in diabetic rats receiving distilled water. It could be concluded that consumption of sucralose didn’t induce oxidative stress, has no effect on insulin, reduce glucose absorption and intensify hypercholesterolemia in STZ-induced diabetic rats. Accordingly it is advised that diabetic people consuming high amount of sucralose must check their lipid profile to avoid diabetic complications.

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H. Saada, N. Mekky, H. Eldawy and A. Abdelaal, "Biological Effect of Sucralose in Diabetic Rats," Food and Nutrition Sciences, Vol. 4 No. 7A, 2013, pp. 82-89. doi: 10.4236/fns.2013.47A010.

References

[1] A. Nakhaee, M. Bokaeian, A. Akbarzadeh and M. Hashemi, “Sodium Tungstate Attenuates Oxidative Stress in Brain Tissue of Streptozotocin-Induced Diabetic Rats,” Biological Trace Element Research, Vol. 136, No. 2, 2010, pp. 221-231. doi:10.1007/s12011-009-8537-0
[2] B. Halliwell and J. M. Gutteridge, “Role of Free Radicals and Catalytic Metal Ions in Human Disease: An Overview,” Methods in Enzymology, Vol. 186, 1990, pp. 1-85. doi:10.1016/0076-6879(90)86093-B
[3] M. Kawamura, J. W. Heinecke and A. Chait, “Pathophysiological Concentrations of Glucose Promote Oxidative Modification of Low Density Lipoprotein by a Superoxide Dependent Pathway,” Journal of Clinical Investigation, Vol. 94, No. 2, 1994, pp. 771-778. doi:10.1172/JCI117396
[4] M. Brownlee, “Biochemistry and Molecular Cell Biology of Diabetic Complications,” Nature, Vol. 414, No. 6865, 2001, pp. 813-820. doi:10.1038/414813a
[5] S. P. Wolff, Z. Y. Jiang and J. V. Hunt, “Protein Glycation and Oxidative Stress in Diabetes Mellitus and Ageing,” Free Radical Biology and Medicine, Vol. 10, No. 5, 1991, pp. 339-352. doi:10.1016/0891-5849(91)90040-A
[6] M. Victor, J. Kenneth and R. Milagros, “Recent Progress in Pharmacological Research of Antioxidants in Pathological Conditions: Cardiovascular Health,” Recent Patents on Anti-Infective Drug Discovery, Vol. 1, No. 1, 2006, pp. 17-31. doi:10.2174/157489106775244136
[7] J. Nordberg and E. S. J. Arner, “Reactive Oxygen Species, Antioxidants, and the Mammalian Thioredoxin System,” Free Radical Biology and Medicine, Vol. 31, No. 11, 2001, pp. 1287-1312. doi:10.1016/S0891-5849(01)00724-9
[8] I. Knight, “The Development and Applications of Sucralose, a New High-Intensity Sweetener,” Canadian Journal of Physiology and Pharmacology, Vol. 72, No. 4, 1993, pp. 435-439. doi:10.1139/y94-063
[9] M. A. Friedman, “Food Additives Permitted for Direct Addition to Food for Human Consumption; Sucralose,” Federal Register: 21 CFR Part 172, Docket No. 87F-0086, 1998.
[10] N. M. Binns, “Sucralose: Alt Sweeteners and Light,” Nutrition Bulletin, Vol. 29, No. 1, 2003, pp. 53-58. doi:10.1046/j.1467-3010.2003.00307.x
[11] Federal Register, “Food Additives Permitted for Direct Addition to Food for Human, Consumption: Sucralose,” Food and Drug Administration, HHS, Final Rule April 3, 1998, Vol. 63, No. 64, Rules and Regulations, pp. 1641716433.
[12] B. A. John, S. G. Wood and D. R. Hawkins, “The Pharmacokinetics and Metabolism of Sucralose in the Mouse,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 107-110. doi:10.1016/S0278-6915(00)00032-6
[13] A. B. Rodero, L. S. Rodero and R. Azoubel, “Toxicity of Sucralose in Humans: A Review,” International Journal of Morphology, Vol. 27, No. 1, 2009, pp. 239-244. doi:10.4067/S0717-95022009000100040
[14] H. C. Grice and L. A. Goldsmith, “Sucralose: An Overview of the Toxicity Data,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 1-6.
[15] L. A. Goldsmith, “Acute and Subchronic Toxicity of Sucralose,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 53-69. doi:10.1016/S0278-6915(00)00028-4
[16] J. P. Finn and G. H. Lord, “Neurotoxicity Studies on Sucralose and Its Hydrolysis Products with Special Reference to Histopathologic and Ultrastructural Changes,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 7-17. doi:10.1016/S0278-6915(00)00024-7
[17] J. W. Kille, W. C Ford, P. McAnulty, J. M. Tesh, F. W. Ross and C. R. Willoughby, “Sucralose: Lack of Effects on Sperm Glycolysis and Reproduction in the Rat,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 1929. doi:10.1016/S0278-6915(00)00025-9
[18] D. Brusick, V. L. Grotz, R. Slesinski, C. L. Kruger and A. W. Hayes, “The Absence Ofgenotoxicity of Sucralose,” Food and Chemical Toxicology, Vol. 48, No. 11, 2010, pp. 3067-3072. doi:10.1016/j.fct.2010.07.047
[19] G. S. Rocha, M. O. Pereira, M. O. Benarroz, J. N. Frydman, V. C. Rocha, M. J. Pereira, A. S. Fonseca, A. C. Medeiros and M. Bernardo-Filho, “Sucralose Sweetener in Vivo Effects on Blood Constituents Radiolabeling, Red Blood Cell Morphology and Radiopharmaceutical Biodistribution in Rats,” Applied Radiation and Isotopes, Vol. 69, No. 1, 2011, pp. 46-51. doi:10.1016/j.apradiso.2010.08.009
[20] R. M. Patel, R. Sarma and E. Grimsley, “Popular Sweetner Sucralose as a Migraine Trigger,” Headache, Vol. 46, No. 8, 2006, pp. 1303-1304. doi:10.1111/j.1526-4610.2006.00543_1.x
[21] M. B. Abou-Donia, E. M. El-Masry, A. A. Abdel-Rahman, R. E. McLendon and S. S. Schiffman, “Splenda Alters Gut Microflora and Increases Intestinal p-Glycoprotein and Cytochrome p-450 in Male Rats,” Journal of Toxicology and Environmental Health, Part A, Vol. 71, No. 21, 2008, pp. 1415-1429. doi:10.1080/15287390802328630
[22] D. Stephen, “Sucralose Safety Scientifically Sound,” Expert panel, 2009. http://www.foodnavigator.com/Science-Nutrition/Sucralose-safety-scientifically-sound-Expert-panel
[23] H. V. Motwani, S. Qiu, B. T. Golding, H. Kylin and M. Tornqvist, “Cob(I) Alamin Reacts with Sucralose to Afford an Alkylcobalamin: Relevance to in Vivo Cobalamin and Sucralose Interaction,” Food and Chemical Toxicology, Vol. 49, No. 4, 2011, pp. 50-57. doi:10.1016/j.fct.2010.11.037
[24] P. Trinder, “Enzymatic Colorimetric Determination of Glucose,” Annals of Clinical Biochemistry, Vol. 6, No. 2, 1969, pp. 24-27.
[25] P. Fossati and L. Prencipe, “Serum Triglycerides Determination Colometrically with an Enzyme Produce Hydrogen Peroxide,” Clinical Chemistry, Vol. 28, No. 10, 1982, p. 2077.
[26] N. Richmond, “Colorimetric Determination of Total Cholesterol and High Density Lipoprotein Cholesterol (HDLC),” Clinical Chemistry, Vol. 19, No. 12, 1973, pp. 13501356.
[27] W. T. Friedewald, R. I. Levy and D. S. Frederickson, “Estimation of the Concentration of Low-Density Lipoprotein Cholesterol in Plasma, without Use of the Preparative Ultracentrifuge,” Clinical Chemistry, Vol. 18, No. 6, 1972, pp. 449-452.
[28] M. Nishikimi, N. A. Rao and K. Yagi, “The Occurrence of Superoxide Anion in the Reaction of Reduced Phenazinemethosulfate and Molecular Oxygen,” Biochemical and Biophysical Research Communications, Vol. 46, No. 2, 1972, pp. 849-854. doi:10.1016/S0006-291X(72)80218-3
[29] H. U. Aebi, “Catalase,” In: H. U. Bergmeyer, Ed., Methods in Enzymatic Analysis, 2nd Edition, Vol. 3, Academic Press, New York, 1983, pp. 276-286.
[30] D. E. Paglia and W. N. Valentine, “Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase,” Journal of Laboratory and Clinical Medicine, Vol. 70, No. 1, 1967, pp. 158-169.
[31] A. Kornberg and B. L. Horecker, “Glucose-6-Phosphate Dehydrogenase,” In: S. Colowick and N. Kaplan, Eds., Methods in Enzymology. I, Academic Press Inc., New York, 1955, pp. 323-325. doi:10.1016/0076-6879(55)01046-X
[32] E. Beutler, O. Duron and B. M. Kelly, “Improved Method for Determination of Blood Glutathione,” Journal of Laboratory and Clinical Medicine, Vol. 61, No. 5, 1963, p. 882.
[33] A. Akbarzadeh, D. Norouzian, M. R. Mehrabi, Sh. Jamshidi, A. Farhangi, A. Allah Verdi, S. M. A. Mofidian and R. B. Lame, “Induction of Diabetes by Streptozotocin in Rats,” Indian Journal of Clinical Biochemistry, Vol. 22, No. 2, 2007, pp. 60-64. doi:10.1007/BF02913315
[34] S. R. F. Tabatabaei, A. A. Papahn, M. R. Jalali and L. Rahimi, “The Effects of Oral Vitamin E on Induction and Consequence of Experimental Diabetes Mellitus in Rats,” Pakistan Journal of Biological Sciences, Vol. 11, No. 4, 2008, pp. 633-637. doi:10.3923/pjbs.2008.633.637
[35] T. K. Bera, D. De, K. Chatterjee, K. M. Ali and D. Ghosh, “Effect of Diashis, a Polyherbal Formulation, in Streptozotocin-Induced Diabetic Male Albino Rats,” International Journal of Ayurveda Research, Vol. 1, No. 1, 2010, pp. 18-24. doi:10.4103/0974-7788.59939
[36] H. E. Ford, V. Peters, N. M. Martin, M. L. Sleeth, M. A. Ghatei, G. S. Frost and S. R. Bloom, “Effects of Oral Ingestion of Sucralose on Gut Hormone Response and Appetite in Healthy Normal-Weight Subjects,” European Journal of Clinical Nutrition, Vol. 65, No. 4, 2011, pp. 508-513. doi:10.1038/ejcn.2010.291
[37] Y. Nakagawa, M. Nagasawa, S. Yamada, A. Hara, H. Mogami, V. O. Nikolaev, M. J. Lohse, N. Shigemura, Y. Ninomiya and I. Kojima, “Sweet Taste Receptor Expressed in Pancreatic β-Cells Activates the Calcium and Cyclic AMP Signaling Systems and Stimulates Insulin Secretion,” PLoS ONE, Vol. 4, No. 4, 2009, p. 5106. doi:10.1371/journal.pone.0005106
[38] J. Ma, J. Chang, H. L. Checklin, R. L. Young, K. L. Jones, M. Horowitz and C. K. Rayner, “Effect of the Artificial Sweetener, Sucralose, on Small Intestinal Glucose Absorption in Healthy Human Subjects,” British Journal of Nutrition, Vol. 104, No. 6, 2010, pp. 803-806. doi:10.1017/S0007114510001327
[39] N. H. Mezitis, C. A. Maggio, P. Koch, A. Quddoos, D. B. Allison and F. X. Pi-Sunyer, “Glycemic Effect of a Single High Oral Dose of the Novel Sweetener Sucralose in Patients with Diabetes,” Diabetes Care, Vol. 19, No. 9, 1996, pp. 1004-1005. doi:10.2337/diacare.19.9.1004
[40] V. L. Grotz, R. R. Henry, J. B. McGill, M. J. Prince, H. Shamoon, J. R. Trout and F. X. Pi-Sunyer, “Lack of Effect of Sucralose on Glucose Homeostasis in Subjects with Type 2 Diabetes,” Journal of the American Dietetic Association, Vol. 103, No. 12, 2003, pp. 1607-1612. doi:10.1016/j.jada.2003.09.021
[41] J. D. Mendez and F. Balderas, “Regulation of Hyperglycemia and Dyslipidemia by Exogenous L-Arginine in Diabetic Rats,” Biochimie, Vol. 83, No. 5, 2001, pp. 453458. doi:10.1016/S0300-9084(00)01192-5
[42] O. Komolafe, D. Adeyemi, S. Adewole and E. Obuotor, “Streptozotocin-Induced Diabetes Alters the Serum Lipid Profiles of Adult Wistar Rats,” The Internet Journal of Cardiovascular Research, Vol. 7, No. 1, 2009, p. 2.
[43] D. Mathe, “Dyslipidemia and Diabetes Animal Models,” Diabetes & Metabolism, Vol. 21, No. 2, 1995, p. 106.
[44] C. F. Semenkovich, M. Wims, L. Noe, J. Etienne and L. Chan, “Insulin Regulation of Lipoprotein Lipase Activity in 3T3-L1 Adipocytes Is Mediated at Posttranscriptional and Posttranslational Levels,” Journal of Biological Chemistry, Vol. 25, No. 15, 1989, pp. 9030-9038.
[45] P. Ferré, “The Biology of Peroxisome Proliferator-Activated Receptors. Relationship with Lipid Metabolism and Insulin Sensitivity,” Diabetes, Vol. 53, No. 1, 2004, pp. 43-50. doi:10.2337/diabetes.53.2007.S43
[46] J. C. Fruchart, B. Staels and P. Duriez, “PPARs, Metabolic Disease and Atherosclerosis,” Pharmacological Research, Vol. 44, No. 5, 2001, pp. 345-352. doi:10.1006/phrs.2001.0871
[47] I. M. Baird, N. W. Shephard, R. J. Merritt and G. HildickSmith, “Repeated Dose Study of Sucralose Tolerance in Human Subjects,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 123-129. doi:10.1016/S0278-6915(00)00035-1
[48] B. Halliwell, “Role of Free Radicals in the Neurodegenerative Diseases: Therapeutic Implications for Antioxidant Treatment,” Drugs & Aging, Vol. 18, No. 9, 2001, pp. 685-716. doi:10.2165/00002512-200118090-00004
[49] R. C. Zangar, D. R. Davydov and S. Verma, “Mechanisms That Regulate Production of Reactive Oxygen Species by Cytochrome P450,” Toxicology and Applied Pharmacology, Vol. 199, No. 3, 2004, pp. 316-331. doi:10.1016/j.taap.2004.01.018
[50] S.-Y. Ou, G. M. Jackson, X. Jiao, J. Chen, J.-Z. Wu and X.-S. Huang, “Protection against Oxidative Stress in Diabetic Rats by Wheat Bran Feruloyl Oligosaccharides,” Journal of Agricultural and Food Chemistry, Vol. 55, No. 8, 2007, pp. 3191-3195. doi:10.1021/jf063310v
[51] A. Armagan, UzEfkan, H. R. Yilmaz, S. Soyupek, T. Oksay and N. Ozcelik, “Effects of Melatonin on Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rat Testis,” Asian Journal of Andrology, Vol. 8, No. 5, 2006, pp. 595-600. doi:10.1111/j.1745-7262.2006.00177.x
[52] M. Aragno, E. Tamagno, V. Gatto, E. Brignardello, S. Parola, O. Danni and G. Boccuzzi, “Dehydroepiandrosterone Protects Tissues of Streptozotocin-Treated Rats against Oxidative Stress,” Free Radical Biology & Medicine, Vol. 26, No. 11-12, 1999, pp. 1467-1474. doi:10.1016/S0891-5849(99)00012-X
[53] M. H. Abdel-Wahab and A. R. Abd-Allah, “Possible Protective Effect of Melatonin and/or Desferrioxamine against Streptozotocin-Induced Hyperglycaemia in Mice,” Pharmacological Research, Vol. 41, No. 5, 2000, pp. 533-537. doi:10.1006/phrs.1999.0614
[54] D. Borenshtein, R. Ofri, M. Werman, A. Stark, H. J. Tritschler, W. Moeller and Z. Madar, “Cataract Development in Diabeticsand Rats Treated with α-Lipoic Acid and Its γ-Linolenic Acid Conjugate,” Diabetes/Metabolism Research and Reviews, Vol. 17, No. 1, 2001, pp. 4450. doi:10.1002/1520-7560(0000)9999:9999<::AID-DMRR153>3.0.CO;2-S
[55] H. G, Zhao, G. W. Liu, S. C. Liu, Z. C. Wang, Y. Liu, Z. Q. Wang, C. Li, L. Cai and S. L. Gong, “Changes of Cycle and Apoptosis of Spermatogenic Cells and Antioxidant Capacity in Male Rats with Diabetes Mellitus,” National Journal of Antrology, Vol. 11, No. 10, 2005, pp. 735-739.
[56] G. Ricci, A. Catizone, R. Esposito, F. A. Pisanti, M. T. Vietri and M. Galdieri, “Diabetic Rat Testes: Morphological and Functional Alterations,” Andrologia, Vol. 41, No. 6, 2009, pp. 361-368. doi:10.1111/j.1439-0272.2009.00937.x
[57] W.-C. Huang, S.-W. Juang, M. Liu, T.-C. Chi and J.-T. Cheng, “Changes of Superoxide Dismutase gene Expression and Activity in the Brain of Streptozotocin-Induced Diabetic Rats,” Neuroscience Letters, Vol. 275, No. 1, 1999, pp. 25-28.
[58] P. Kaur, G. Kaur and M. P. Bansal, “Tertiary-Butyl Hydroperoxide Induced Oxidative Stress and Male Reproductive Activity in Mice: Role of Transcription Factor NF-KappaB and Testicular Antioxidant Enzymes,” Reproductive Toxicology, Vol. 22, No. 3, 2006, pp. 479-484. doi:10.1016/j.reprotox.2006.03.017
[59] H. C. Grice and L. A. Goldsmith, “Sucralose: An Overview of the Toxicity Data,” Food and Chemical Toxicology, Vol. 38, No. 2, 2000, pp. 1-6. doi:10.1016/S0278-6915(00)00023-5

  
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