Clinical Research
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Year 2022, , 232 - 237, 31.12.2022
https://doi.org/10.26650/experimed.1192759

Abstract

Supporting Institution

YOK

Project Number

YOK

References

  • 1. Soffritti M, Padovani M, Tibaldi E, Fabiana L, Manservisi F, Belpoggi F. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation. Am J Ind Med 2014; 57(4): 383-97. [CrossRef] google scholar
  • 2. "Aspartame". PubChem, National Library of Medicine, US National Institutes of Health. 17 August 2019. google scholar
  • 3. Whitehouse RC, Boullata J, McCauley AL. The potential toxicity of artificial sweeteners. AAOHN J 2008; 56(6): 251-9. [CrossRef] google scholar
  • 4. Benford D. Report of the meetings on aspartame with national experts. EFSA Supporting Publications. EFSA. Noted at the 36th Advisory Forum Meeting, 19-20 May, 2010. google scholar
  • 5. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et.al. Aspartame: Review of safety. Regul Toxicol Pharmacol 2002; 35(2 Pt 2): S1-93. [CrossRef] google scholar
  • 6. Harriett H, Butchko and Stargely WW. Aspartame: Scientific Evaluation in the Postmarketing Period. Regul Toxicol Pharmacol 2001; 34, 221-233. [CrossRef] google scholar
  • 7. Gombos K, Varjas T, Orsos Z, Polyak E, Peredi J, Varga Z, et al. The effect of aspartame administration on oncogene and suppressor gene expressions In Vivo, 2007; 21(1): 89-92. google scholar
  • 8. Ells JT, Henry MM, Lewandowski MF, Seme MT and Murray T. Development and characterization of a rodent model of methanol-induced retinal and optic nerve toxicity. Neurotoxicology 2000; 21(3): 321-30. google scholar
  • 9. Prokic MD, Paunovic MG, Matic MM, Djordjevic NZ, Ognjanovic BI, Stajn AS, et al. Prooxidative effects of aspartame on antioxidant defense status in erythrocytes of rats. J Biosci 2014; 39(5): 859-66. [CrossRef] google scholar
  • 10. Parthasarathy JN, Ramasundaram SK, Sundaramahalingam M and Pathinasamy SD. Methanol induced oxidative stress in rat lymphoid organs. J Occup Health 2006; 48(1): 20-7. [CrossRef] google scholar
  • 11. Choudhary AK and Devi RS. Imbalance of the oxidant-antioxidant status by aspartame in the organs of immune system of Wistar albino rats. Afr J Pharm Pharmacol 2014; 8: 220-30. [CrossRef] google scholar
  • 12. Choudhary AK, Sheela Devi R. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats. Endocrinol Nutr 2015; 62(3): 114-22. [CrossRef] google scholar
  • 13. Parola, M., and Robino, G. Oxidative stress-related molecules and liver fibrosis. J Hepatology 2001; 35(2): 297-306. [CrossRef] google scholar
  • 14. Humphries, P, Pretorius E, Naude H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr 2008; 62(4): 45162. [CrossRef] google scholar
  • 15. Olney JW, Farber NB, Spitznagel E, Robins LN. Increasing brain cancer rates: is there a link to aspartame? J. Neuropathol Exp Neurol 1996; 55 (11): 1115-23. [CrossRef] google scholar
  • 16. Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr 2012; 96(6), 1419-28. [CrossRef] google scholar
  • 17. FDA. Food additives permitted for direct addition to food for human consumption; aspartame. Food and Drug Administration. Federal Register I Vol. 48. No. 132 I Friday. July 8. 1983 I Rules and Regulations. google scholar
  • 18. Nau H. Species differences in pharmacokinetics and drug teratogenesis. Environ Health Perspect 1986; 70: 113-29. [CrossRef] google scholar
  • 19. Denes V, Agoston DV. How to translate time? The temporal aspect of human and rodent biology. Front Neurol 2017; 8: 92. [CrossRef] google scholar
  • 20. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, et al. Aspartame: a safety elevation based on current use levels, regulations, andtoxicological and epidemiological studies. Crit Rev Toxicol 2008; 629-727. [CrossRef] google scholar
  • 21. Brancatelli G, Furlan A, Calandra A and Burgio MD. Hepatic sinusoidal dilatation. Abdom Radiol (NY) 2018; 43(8), 2011-22. [CrossRef] google scholar
  • 22. Li MK, Crawford JM. The pathology of cholestasis. Semin Liver Dis 2004; 24(1): 21-42. [CrossRef] google scholar
  • 23. Mohamed AL, Hossam GT , Yasser SS. Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status. Nutr Res 2017; 41: 47-55. [CrossRef] google scholar
  • 24. Finamor IA, Bressan CA, Torres-Cuevas I, Rius-Pérez S, Veiga M, Rocha MI, et al. Long-term aspartame administration leads to fibrosis, inflammasome activation, and gluconeogenesis impairment in the liver of mice. Biology (Basel) 2021; 10(2): 82. [CrossRef] google scholar
  • 25. Ashok I, Sheeladevi R. Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame. J Food Drug Anal 2015; 23(4): 679-91. [CrossRef] google scholar
  • 26. Horio Y, Sun Y, Liu C, Saito T, Kurasaki M. Aspartame-induced apoptosis in PC12 cells. Environ Toxicol Pharmacol 2014; 37(1): 158-65. [CrossRef] google scholar

Clues to the Harmful Effects of Aspartame on Liver Morphology and Function

Year 2022, , 232 - 237, 31.12.2022
https://doi.org/10.26650/experimed.1192759

Abstract

Objective: Aspartame is a widely used artificial sweetener that was approved by the United States Food and Drug Administration (FDA) in 1996 for use as a general sweetener in all foods. Previous studies on aspartame had suggested it to be non-toxic. However, some studies have reported it to have carcinogenic, neurotoxic, apoptotic, and inflammatory effects. The knowledge obtained from previous studies has been insufficient and contradictory, thus the aim of this study was to demonstrate the harmful side effects of daily and high doses of aspartame on the rat livers.

Materials and Methods: The study separated 18 Long Evans rats weighing between 250-300g into three groups: control, low dosage, and high dosage groups (n = 6 in each). 50 mg/kg of aspartame was given to the low dose group and 250 mg/kg to the high dose group every day for 10 weeks. At the end of the 10th week, all groups were euthanized and their livers and blood samples collected. Liver tissues were subjected to hematoxylin-eosin and Masson’s trichome staining, after which terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunohistochemistry was performed to check the serum alanine transaminase (ALT) and aspartate transaminase (AST) values. The enzyme-linked immunosorbent assay (ELISA) method was applied for analyzing superoxide dismutase (SOD) and malondialdehyde (MDA) levels.

Results: Enlargement of the bile canaliculi and dilatation of sinusoids were observed in the group that was given high doses of aspartame. At the same time, the amount of TUNEL-positive cells was higher in the high dose group. AST, ALT, and MDA values were increased while SOD values were decreased in both the low and high aspartame dosage groups.

Conclusion: This study has concluded the prolonged use of high doses of aspartame to be able to cause damage to hepatocytes by stimulating oxidative stress, hepatocyte apoptosis, and necrosis.

Project Number

YOK

References

  • 1. Soffritti M, Padovani M, Tibaldi E, Fabiana L, Manservisi F, Belpoggi F. The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation. Am J Ind Med 2014; 57(4): 383-97. [CrossRef] google scholar
  • 2. "Aspartame". PubChem, National Library of Medicine, US National Institutes of Health. 17 August 2019. google scholar
  • 3. Whitehouse RC, Boullata J, McCauley AL. The potential toxicity of artificial sweeteners. AAOHN J 2008; 56(6): 251-9. [CrossRef] google scholar
  • 4. Benford D. Report of the meetings on aspartame with national experts. EFSA Supporting Publications. EFSA. Noted at the 36th Advisory Forum Meeting, 19-20 May, 2010. google scholar
  • 5. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL, et.al. Aspartame: Review of safety. Regul Toxicol Pharmacol 2002; 35(2 Pt 2): S1-93. [CrossRef] google scholar
  • 6. Harriett H, Butchko and Stargely WW. Aspartame: Scientific Evaluation in the Postmarketing Period. Regul Toxicol Pharmacol 2001; 34, 221-233. [CrossRef] google scholar
  • 7. Gombos K, Varjas T, Orsos Z, Polyak E, Peredi J, Varga Z, et al. The effect of aspartame administration on oncogene and suppressor gene expressions In Vivo, 2007; 21(1): 89-92. google scholar
  • 8. Ells JT, Henry MM, Lewandowski MF, Seme MT and Murray T. Development and characterization of a rodent model of methanol-induced retinal and optic nerve toxicity. Neurotoxicology 2000; 21(3): 321-30. google scholar
  • 9. Prokic MD, Paunovic MG, Matic MM, Djordjevic NZ, Ognjanovic BI, Stajn AS, et al. Prooxidative effects of aspartame on antioxidant defense status in erythrocytes of rats. J Biosci 2014; 39(5): 859-66. [CrossRef] google scholar
  • 10. Parthasarathy JN, Ramasundaram SK, Sundaramahalingam M and Pathinasamy SD. Methanol induced oxidative stress in rat lymphoid organs. J Occup Health 2006; 48(1): 20-7. [CrossRef] google scholar
  • 11. Choudhary AK and Devi RS. Imbalance of the oxidant-antioxidant status by aspartame in the organs of immune system of Wistar albino rats. Afr J Pharm Pharmacol 2014; 8: 220-30. [CrossRef] google scholar
  • 12. Choudhary AK, Sheela Devi R. Longer period of oral administration of aspartame on cytokine response in Wistar albino rats. Endocrinol Nutr 2015; 62(3): 114-22. [CrossRef] google scholar
  • 13. Parola, M., and Robino, G. Oxidative stress-related molecules and liver fibrosis. J Hepatology 2001; 35(2): 297-306. [CrossRef] google scholar
  • 14. Humphries, P, Pretorius E, Naude H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr 2008; 62(4): 45162. [CrossRef] google scholar
  • 15. Olney JW, Farber NB, Spitznagel E, Robins LN. Increasing brain cancer rates: is there a link to aspartame? J. Neuropathol Exp Neurol 1996; 55 (11): 1115-23. [CrossRef] google scholar
  • 16. Schernhammer ES, Bertrand KA, Birmann BM, Sampson L, Willett WC, Feskanich D. Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. Am J Clin Nutr 2012; 96(6), 1419-28. [CrossRef] google scholar
  • 17. FDA. Food additives permitted for direct addition to food for human consumption; aspartame. Food and Drug Administration. Federal Register I Vol. 48. No. 132 I Friday. July 8. 1983 I Rules and Regulations. google scholar
  • 18. Nau H. Species differences in pharmacokinetics and drug teratogenesis. Environ Health Perspect 1986; 70: 113-29. [CrossRef] google scholar
  • 19. Denes V, Agoston DV. How to translate time? The temporal aspect of human and rodent biology. Front Neurol 2017; 8: 92. [CrossRef] google scholar
  • 20. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, et al. Aspartame: a safety elevation based on current use levels, regulations, andtoxicological and epidemiological studies. Crit Rev Toxicol 2008; 629-727. [CrossRef] google scholar
  • 21. Brancatelli G, Furlan A, Calandra A and Burgio MD. Hepatic sinusoidal dilatation. Abdom Radiol (NY) 2018; 43(8), 2011-22. [CrossRef] google scholar
  • 22. Li MK, Crawford JM. The pathology of cholestasis. Semin Liver Dis 2004; 24(1): 21-42. [CrossRef] google scholar
  • 23. Mohamed AL, Hossam GT , Yasser SS. Long-term soft drink and aspartame intake induces hepatic damage via dysregulation of adipocytokines and alteration of the lipid profile and antioxidant status. Nutr Res 2017; 41: 47-55. [CrossRef] google scholar
  • 24. Finamor IA, Bressan CA, Torres-Cuevas I, Rius-Pérez S, Veiga M, Rocha MI, et al. Long-term aspartame administration leads to fibrosis, inflammasome activation, and gluconeogenesis impairment in the liver of mice. Biology (Basel) 2021; 10(2): 82. [CrossRef] google scholar
  • 25. Ashok I, Sheeladevi R. Oxidant stress evoked damage in rat hepatocyte leading to triggered nitric oxide synthase (NOS) levels on long term consumption of aspartame. J Food Drug Anal 2015; 23(4): 679-91. [CrossRef] google scholar
  • 26. Horio Y, Sun Y, Liu C, Saito T, Kurasaki M. Aspartame-induced apoptosis in PC12 cells. Environ Toxicol Pharmacol 2014; 37(1): 158-65. [CrossRef] google scholar
There are 26 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Emine Rümeysa Hekimoğlu 0000-0003-4300-7213

Birsen Elibol 0000-0002-9462-0862

Ceyhun Toruntay 0000-0002-4743-0257

Seda Kırmızıkan 0000-0002-5652-778X

Ozge Pasin 0000-0001-6530-0942

Ufuk Sarıkaya 0000-0003-4573-5505

Damla Alkhalidi 0000-0001-8553-659X

Mukaddes Eşrefoğlu 0000-0003-3380-1480

Project Number YOK
Publication Date December 31, 2022
Submission Date October 24, 2022
Published in Issue Year 2022

Cite

Vancouver Hekimoğlu ER, Elibol B, Toruntay C, Kırmızıkan S, Pasin O, Sarıkaya U, Alkhalidi D, Eşrefoğlu M. Clues to the Harmful Effects of Aspartame on Liver Morphology and Function. Experimed. 2022;12(3):232-7.