حامد نصیری
1
(دانش‌آموخته دکترای حرفه‌ای، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.)
جعفر رحمانی کهنموئی
2
(استادیار گروه علوم درمانگاهی، دانشکده دامپزشکی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران.)
چکیده مقاله :
سوکرالوز شیرین‌کننده مصنوعی مشتق از ساکارز می‌باشد که 600 بار از شکر شیرین‌تر می‌باشد ولی کالری کمی ایجاد می‌کند. Ciplaبه عنوان یک شیرین‌کننده تجاری علاوه بر سوکرالوز، واجد ترکیبات مختلفی همچون لاکتوز و اِل لوسین نیز می‌باشد. هدف از مطالعه حاضر بررسی تاثیر استفاده از Cipla بر پروتئین‌های سرم در موش های صحرایی سالم و دیابتی شده بود. تعداد 24 سر موش صحرایی نر انتخاب و به صورت تصادفی به 4 گروه مساوی شاهد سالم، شاهد دیابتی، تیمار سالم و تیمار دیابتی شده تقسیم شدند. گروه های شاهد سالم و شاهد دیابتی جیره پایه و گروه های تیمار سالم و تیمار دیابتی شده، روزانه و به‌مدت یک‌ماه Ciplaبا دوز mg/kg 15 از طریق گاواژ دریافت کردند. در طی دوره آزمایش شرایط یکسان محیطی برای همه گروه‌ها اعمال شد. پس از اتمام دوره آزمایش ، از همه موش ها خون گیری انجام گرفته و بعد از جداسازی سرم، با روش الکتروفورز استات سلولز، منحنی الکتروفورز پروتئین‌های سرم تهیه و مورد بررسی قرار گرفت. میزان پروتئین تام و آلبومین سرم در حیوانات گروه های تیمار سالم و شاهد دیابتی به طور غیرمعنی‌داری (05/0p >) بیشتر از میزان آن ها در سرم موش های بقیه گروه‌ها بود ولی میزان آلفا1 گلبولین در سرم موش های گروه شاهد سالم به طور معنی‌داری (05/0> p ) پائین‌تر از میزان آن در سرم حیوانات گروه های شاهد دیابتی و تیمار سالم برآورد شد. همچنین میزان آلفا2 گلبولین و بتاگلبولین به طور غیرمعنی‌داری (05/0p >) در سرم حیوانات گروه های تیمار دیابتی شده و تیمار سالم بالاتر از میزان آن ها در سرم موش های هر دو گروه شاهد سالم و شاهد دیابتی بود. از لحاظ میزان گاماگلبولین سرم نیز اختلاف آماری معنی‌داری در بین گروه های مورد مطالعه وجود نداشت (05/0p >). به نظر می رسد که مصرفCiplaبه غیر از مقدار آلفا1 گلوبولین، تاثیر چندانی بر منحنی الکتروفورتیک پروتئین‌های سرم موش صحرائی ندارد.
چکیده انگلیسی:
Introduction: Sucralose is an artificial sweetener without calorie that derived from sugar or sucrose. It is 600 times sweeter than sugar also makes low calorie. Cipla as a commercial sweetener have different compounds such as, lactose, L-lusin, Cross Carmellose Sodium. Sucralose is stable in the presence of ethanol and can retain 99% of its true taste after one year, as well as maintain its properties during pasteurization, sterilization, and high temperature baking. It also does not interfere with glucose uptake, carbohydrate metabolism or insulin secretion. Pharmacokinetic studies have shown that 85% of sucralose is not absorbed and is completely excreted through the stool and its absorption rate is limited to 15% in passive release. Recent studies have shown a link between the use of sweeteners and renal toxicity, hepatotoxicity or retardation of fetal and placenta formation. Sucralose is converted to hydrolysis products 4- Chloro glucose and 1,6 di chlorofructose by hydrolysis. These metabolites are more resistant to hydrolysis and complete degradation as sucrose chlorination and conversion to sucralose alter the conversion of the molecule to glycosidic enzymes. The digestive tract, which normally breaks down carbohydrates, becomes. In a double-blind study by Grots et al., it was found that sucralose at a dose of 7.5 mg/ kg/day for one month had no significant effect on serum glucose and HbA1c levels in humans. Other studies on non-diabetic human specimens have shown that high doses of sucralose or aspartame do not affect blood glucose, peptide c, or hemoglobin levels of HbA1c, even at multiple doses. According to conflicting reports on the metabolic effects of sweeteners, the study assessed the effect of using the commercial form of sucralose (Cipla) on serum electrophoretic proteins in healthy and diabetic rats.Materials and methods: This study will be done on 24 male rats divided in four equal groups, control and treatment. Control group will have base ration. In the study of Shastry and et al, is 15mg/kg for human. Therefore, in this study dosage of sucralose will be 15mg/kg. Treatment group will be injected daily for 1-month. All rats used for this study have same peripheral conditions .At the end of the experimental period, all rat were bled, and after serum isolation, the serum protein electrophoresis curve was prepared and evaluated by acetate cellulose technique.Results and discussion:The amount of total protein and serum albumin was recorded in the healthy treatment group (7.18±0.22 g/dl) and (3.36±0.11 g/dl), in the diabetic control group (7.16±0.18 g/dl) and (3.41±0.09 g/dl), but with the amount of these factors in the serum of other study groups, there was no statistically significant difference (p>0.05). The amount of alpha 1 globulin in the serum of healthy control group (0.01±0.30 g/dl) was significantly lower than the rate of this factor in animal serum of diabetic control group (0.04±0.51 g/dl) and healthy treatment group (0.03±0.46 g/dl) (p 0.05). Gammaglobulin levels were determined in the healthy treatment group (1.20±0.12 g/dl), diabetic treatment (1.10±0.21 g/dl), healthy control group (1.33±0.14 g/dl) and diabetic control group (1.25±0.08 g/dl), Which showed a no significant statistical difference between the studied groups (p>0.05). The study showed that the use of aspartame, acesulfam, and sucralose sweeteners in acceptable daily intake (ADI) doses for three weeks did not have a mutagenic effect on healthy and diabetic rats and had no effect on serum factors which is consistent with the results of the present study. This study demonstrated a significant change in the alpha 1 globulin band in the electrophoretic curve. The bulk of this protein bond is made up of the alpha protein an antitrypsin, a single-chain glycoprotein consisting of 394 amino acids that has a molecular mass of about 52 kDa and easily passes through interstitial fluid to the target tissues. This protein has a negative charge and cannot pass through the glomerular membrane of the kidney. This protein is one of the most important inhibitors of serum human serum proteases and inhibits several proteins such as elastase, collagenase and trypsin. Diabeticization of the animals tested, as well as the consumption of sweeteners, appear to accelerate the production of acute phase proteins, increasing alpha 1 globulin in the electrophoretic curve.Conclusion: The results of this study showed no change in protein bands other than alpha 1 globulin. Therefore, it can be said that sucralose has little effect on the electrophoretic curve of serum proteins.Keywords: Cipla, Electrophoretic curve, Rat, Serum protein, Sucralose.
منابع و مأخذ:
Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E. and Schiffman, S.S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats Journal of Toxicology and Environmental Health, 71(21):1415-1429.
Arruda, J., Martins, A.T. and Azoubel, R. (2003). Sodium cyclamate and fetal kidney. Infant, 3(2): 147-150.
Baird, I.M., Shephard, N., Merritt, R. and Hildick-Smith, G. (2000). Repeated dose study of sucralose tolerance in human subjects. Food and Chemical Toxicology, 38(2): 123-129.
Barndt, R. and Jackson, G. (1990). Stability of sucralose in baked goods. Food Technology, 44: 62-66.
Binns, N.M. (2003). Sucralose–all sweetness and light. Nutrition Bulletin, 28(1): 53-58.
Brown, R.J., De Banate, M.A. and Rother, K.I. (2010). Artificial sweeteners: a systematic review of metabolic effects in youth. International Journal of Paediatric Obesity, 5(4): 305-312.
Davidson, T., Sample, C. and Swithers, S. (2014). An application of Pavlovian principles to the problems of obesity and cognitive decline. Neurobiology of Learning and Memory, 108: 172-184.
De Koning, L., Malik, V.S., Rimm, E.B., Willett, W.C. and Hu, F.B. (2011). Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. The American Journal of Clinical Nutrition, 93(6): 1321-1327.
De Matos, M.A., Martins, A.T. and Azoubel, R. (2006). Effects of sodium cyclamate on the rat placenta: A morphometric study. International Journal of Morphology, 24(2): 137-142.
Dhingra, R., Sullivan, L., Jacques, P.F., Wang, T.J., Fox, C.S., Meigs, J.B., et al. (2007). Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation, 116(5): 480-488.
Fagherazzi, G., Vilier, A., Sartorelli, D.S., Lajous, M., Balkau, B. and Clavel-Chapelon, F. (2013). Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes. The American Journal of Clinical Nutrition, 97(3): 517-523.
Fowler, S.P., Williams, K., Resendez, R.G., Hunt, K.J., Hazuda, H.P. and Stern, M.P. (2008). Artificially sweetened beverage use and long‐term weight gain. Obesity, 16(8):1894-1900.
Goldsmith, L.A. and Meckel, C.M. (2000). Alternative Sweeteners. 3rd ed., New York: Marcel Dekker, pp: 185-207.
Grotz, V.L., Henry, R.R., McGill, J.B., Prince, M.J., Shamoon, H., Trout, J.R., et al. (2003). Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Journal of the American Dietetic Association, 103(12): 1607-1612.
Hassanpour, A., Alipour, K.H. and Moghaddam, S. (2018). Evaluation of serum concentration of haptoglobin and amyloid A in horses with gorm. Journal of Veterinary Clinical Pathology, 11(3): 277-284. [In Persian]
Jang, H.J., Kokrashvili, Z., Theodorakis, M.J., Carlson, O.D., Kim, B.J., Zhou, J., et al. (2007). Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proceedings of the National Academy of Sciences, 104(38): 15069-15074.
Kyriazis, G.A., Soundarapandian, M.M. and Tyrberg, B. (2012). Sweet taste receptor signalling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proceedings of the National Academy of Sciences, 109(8): E524-E532.
Lutsey, P.L., Steffen, L.M. and Stevens, J. (2008). Dietary intake and the development of the metabolic syndrome. Circulation, 117(6): 754-761.
Martins, A.T., Azoubel, R., Lopes, R.A., di Matteo, M.A.S. and de Arruda, J.G.F. (2005). Effect of sodium cyclamate on the rat fetal liver. International Journal of Morphology, 23(3): 221-226.
Mezitis, N.H., Maggio, C.A., Koch, P., Quddoos, A., Allison, D.B. and Pi-Sunyer, F.X. (1996). Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care, 19(9): 1004-1005.
Modaresi, M. (2011). The effect of cinnamon extract on serum proteins levels of male Balb/c mice. Armaghane Danesh, 16(5): 444-452. [In Persian]
Mohajeri, D., Mousavi, Ga. and Mohammadi, P. (2012). Histopathological study of the effect of alcoholic extract of turnip root on ischemia-reperfusion injury in rat. Journal of Veterinary Clinical Pathology, 6(2): 1549-1559. [In Persian]
Nakagawa, Y., Nagasawa, M., Yamada, S., Hara, A., Mogami, H., Nikolaev, V.O., et al. (2009). Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PloS one, 4(4): e5106.
Nasirzadeh, M.R. and Rahmani-Khanmoei, J. (2019). Biochemical effects of alcoholic extract of olive leaf in ovariectomized rats. Journal of Veterinary Clinical Pathology, 12(3): 233-241. [In Persian]
Nehrling, J.K., Kobe, P., McLane, M.P., Olson, R.E., Kamath, S. and Horwitz, D.L. (1985). Aspartame use by persons with diabetes. Diabetes Care, 8(5): 415-417.
Nematollahi, A. and Jafari, R. (2012). Biochemical changes of sheep blood serum in
gastrointestinal nematodes. Journal of Veterinary Clinical Pathology, 6(4): 1697-1701. [In Persian]
Nettleton, J.A., Lutsey, P.L., Wang, Y., Lima, J.A., Michos, E.D. and Jacobs, D.R. (2009). Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care, 32(4): 688-694.
Palmnäs, M.S., Cowan, T.E., Bomhof, M.R., Su, J., Reimer, R.A., Vogel, H.J., et al. (2014). Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PloS one, 9(10): e109841.
Portela, G. and Azoubel, R. (2004). Toxicity of sucralose in humans. International Journal of Morphology, 26(1): 12-18.
Rahmani-Khanmoei, J. (2016). The effect of inactivated inhaled cigarette smoke on serum lipid profile in rats. Journal of Veterinary Clinical Pathology, 10(3): 245-250. [In Persian]
Rahmani-Khanmoei, J. and Asadi, G. (2016). The Effect of Commercial Sweetener “Cipla” on the Serum Lipid Profiles in Diabetes-Induced Rats. Crescent Journal of Medical and Biological Sciences, 3(4): 136-138.
Rahmani-Khanmoei, J. and Ranjbar, A. (2014). Comparative study of the effect of sucralose and sugar on some serum biomarkers of rat. Indian Journal of Fundamental and Applied Life Sciences, 4(1): 10-15.
Rodero, A.B., Rodero, L.D.S. and Azoubel, R. (2009). Toxicity of sucralose in humans: a review. International Journal of Morphology, 27(1): 239-244.
Shastry, C., Yatheesh, C. and Aswathanarayana, B. (2012). Comparative evaluation of diabetogenic and mutagenic potential of artificial sweeteners-aspartame, acesulfame-K and sucralose. Nitte University Journal of Health Science, 2(3): 80-81.
Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C.A., Maza, O., et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521): 181-186.
Swithers, S.E., Martin, A.A. and Davidson, T.L. (2010). High-intensity sweeteners and energy balance. Physiology and Behaviour, 100(1): 55-62.
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Abou-Donia, M. B., El-Masry, E. M., Abdel-Rahman, A. A., McLendon, R. E. and Schiffman, S.S. (2008). Splenda alters gut microflora and increases intestinal p-glycoprotein and cytochrome p-450 in male rats Journal of Toxicology and Environmental Health, 71(21):1415-1429.
Arruda, J., Martins, A.T. and Azoubel, R. (2003). Sodium cyclamate and fetal kidney. Infant, 3(2): 147-150.
Baird, I.M., Shephard, N., Merritt, R. and Hildick-Smith, G. (2000). Repeated dose study of sucralose tolerance in human subjects. Food and Chemical Toxicology, 38(2): 123-129.
Barndt, R. and Jackson, G. (1990). Stability of sucralose in baked goods. Food Technology, 44: 62-66.
Binns, N.M. (2003). Sucralose–all sweetness and light. Nutrition Bulletin, 28(1): 53-58.
Brown, R.J., De Banate, M.A. and Rother, K.I. (2010). Artificial sweeteners: a systematic review of metabolic effects in youth. International Journal of Paediatric Obesity, 5(4): 305-312.
Davidson, T., Sample, C. and Swithers, S. (2014). An application of Pavlovian principles to the problems of obesity and cognitive decline. Neurobiology of Learning and Memory, 108: 172-184.
De Koning, L., Malik, V.S., Rimm, E.B., Willett, W.C. and Hu, F.B. (2011). Sugar-sweetened and artificially sweetened beverage consumption and risk of type 2 diabetes in men. The American Journal of Clinical Nutrition, 93(6): 1321-1327.
De Matos, M.A., Martins, A.T. and Azoubel, R. (2006). Effects of sodium cyclamate on the rat placenta: A morphometric study. International Journal of Morphology, 24(2): 137-142.
Dhingra, R., Sullivan, L., Jacques, P.F., Wang, T.J., Fox, C.S., Meigs, J.B., et al. (2007). Soft drink consumption and risk of developing cardiometabolic risk factors and the metabolic syndrome in middle-aged adults in the community. Circulation, 116(5): 480-488.
Fagherazzi, G., Vilier, A., Sartorelli, D.S., Lajous, M., Balkau, B. and Clavel-Chapelon, F. (2013). Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes. The American Journal of Clinical Nutrition, 97(3): 517-523.
Fowler, S.P., Williams, K., Resendez, R.G., Hunt, K.J., Hazuda, H.P. and Stern, M.P. (2008). Artificially sweetened beverage use and long‐term weight gain. Obesity, 16(8):1894-1900.
Goldsmith, L.A. and Meckel, C.M. (2000). Alternative Sweeteners. 3rd ed., New York: Marcel Dekker, pp: 185-207.
Grotz, V.L., Henry, R.R., McGill, J.B., Prince, M.J., Shamoon, H., Trout, J.R., et al. (2003). Lack of effect of sucralose on glucose homeostasis in subjects with type 2 diabetes. Journal of the American Dietetic Association, 103(12): 1607-1612.
Hassanpour, A., Alipour, K.H. and Moghaddam, S. (2018). Evaluation of serum concentration of haptoglobin and amyloid A in horses with gorm. Journal of Veterinary Clinical Pathology, 11(3): 277-284. [In Persian]
Jang, H.J., Kokrashvili, Z., Theodorakis, M.J., Carlson, O.D., Kim, B.J., Zhou, J., et al. (2007). Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proceedings of the National Academy of Sciences, 104(38): 15069-15074.
Kyriazis, G.A., Soundarapandian, M.M. and Tyrberg, B. (2012). Sweet taste receptor signalling in beta cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proceedings of the National Academy of Sciences, 109(8): E524-E532.
Lutsey, P.L., Steffen, L.M. and Stevens, J. (2008). Dietary intake and the development of the metabolic syndrome. Circulation, 117(6): 754-761.
Martins, A.T., Azoubel, R., Lopes, R.A., di Matteo, M.A.S. and de Arruda, J.G.F. (2005). Effect of sodium cyclamate on the rat fetal liver. International Journal of Morphology, 23(3): 221-226.
Mezitis, N.H., Maggio, C.A., Koch, P., Quddoos, A., Allison, D.B. and Pi-Sunyer, F.X. (1996). Glycemic effect of a single high oral dose of the novel sweetener sucralose in patients with diabetes. Diabetes Care, 19(9): 1004-1005.
Modaresi, M. (2011). The effect of cinnamon extract on serum proteins levels of male Balb/c mice. Armaghane Danesh, 16(5): 444-452. [In Persian]
Mohajeri, D., Mousavi, Ga. and Mohammadi, P. (2012). Histopathological study of the effect of alcoholic extract of turnip root on ischemia-reperfusion injury in rat. Journal of Veterinary Clinical Pathology, 6(2): 1549-1559. [In Persian]
Nakagawa, Y., Nagasawa, M., Yamada, S., Hara, A., Mogami, H., Nikolaev, V.O., et al. (2009). Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PloS one, 4(4): e5106.
Nasirzadeh, M.R. and Rahmani-Khanmoei, J. (2019). Biochemical effects of alcoholic extract of olive leaf in ovariectomized rats. Journal of Veterinary Clinical Pathology, 12(3): 233-241. [In Persian]
Nehrling, J.K., Kobe, P., McLane, M.P., Olson, R.E., Kamath, S. and Horwitz, D.L. (1985). Aspartame use by persons with diabetes. Diabetes Care, 8(5): 415-417.
Nematollahi, A. and Jafari, R. (2012). Biochemical changes of sheep blood serum in
gastrointestinal nematodes. Journal of Veterinary Clinical Pathology, 6(4): 1697-1701. [In Persian]
Nettleton, J.A., Lutsey, P.L., Wang, Y., Lima, J.A., Michos, E.D. and Jacobs, D.R. (2009). Diet soda intake and risk of incident metabolic syndrome and type 2 diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care, 32(4): 688-694.
Palmnäs, M.S., Cowan, T.E., Bomhof, M.R., Su, J., Reimer, R.A., Vogel, H.J., et al. (2014). Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat. PloS one, 9(10): e109841.
Portela, G. and Azoubel, R. (2004). Toxicity of sucralose in humans. International Journal of Morphology, 26(1): 12-18.
Rahmani-Khanmoei, J. (2016). The effect of inactivated inhaled cigarette smoke on serum lipid profile in rats. Journal of Veterinary Clinical Pathology, 10(3): 245-250. [In Persian]
Rahmani-Khanmoei, J. and Asadi, G. (2016). The Effect of Commercial Sweetener “Cipla” on the Serum Lipid Profiles in Diabetes-Induced Rats. Crescent Journal of Medical and Biological Sciences, 3(4): 136-138.
Rahmani-Khanmoei, J. and Ranjbar, A. (2014). Comparative study of the effect of sucralose and sugar on some serum biomarkers of rat. Indian Journal of Fundamental and Applied Life Sciences, 4(1): 10-15.
Rodero, A.B., Rodero, L.D.S. and Azoubel, R. (2009). Toxicity of sucralose in humans: a review. International Journal of Morphology, 27(1): 239-244.
Shastry, C., Yatheesh, C. and Aswathanarayana, B. (2012). Comparative evaluation of diabetogenic and mutagenic potential of artificial sweeteners-aspartame, acesulfame-K and sucralose. Nitte University Journal of Health Science, 2(3): 80-81.
Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C.A., Maza, O., et al. (2014). Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature, 514(7521): 181-186.
Swithers, S.E., Martin, A.A. and Davidson, T.L. (2010). High-intensity sweeteners and energy balance. Physiology and Behaviour, 100(1): 55-62.
