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

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

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.

___

  • 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
Experimed-Cover
  • Yayın Aralığı: Yılda 3 Sayı
  • Başlangıç: 2011
  • Yayıncı: İstanbul Üniversitesi
Sayıdaki Diğer Makaleler

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

Emine Rümeysa HEKİMOĞLU, Birsen ELİBOL, Ceyhun TORUNTAY, Seda KIRMIZIKAN, Ozge PASİN, Ufuk SARIKAYA, Damla ALKHALİDİ, Mukaddes EŞREFOĞLU

Activation-Induced Cytidine Deaminase Expression in Patients with Chronic Myeloid Leukemia

Emin OGUZ, Aynur DAĞLAR ADAY, Akif Selim YAVUZ

A Histological Evaluation of the Effect of Ghrelin on Wound Healing in Rats

Esin AK, Kerime ULUSOY-DAG, Feriha ERCAN, Ahmet CORAK

Comparing the VDR Gene BsmI and CDX2Polymorphisms in Healthy Turks and Healthy Somalians Living in Turkiye

Ender COŞKUNPINAR, Betul Nılgun ENGIN

Evaluating the Long-Term Outcomes of Medical and Surgical Treatments in Fibrostenotic Crohn’s Disease Patients Treated with Anti-TNF/Biologic Therapy

Çağatay AK, Süleyman SAYAR, Resul KAHRAMAN, Kamil OZDİL

Cerrahpaşa Medical Faculty Hospital HIV-1/-2 Serological Test Data: 2019-2022 Retrospective Evaluation

Harika Öykü DİNÇ, Elif KESKİN, Banu TUFAN KOÇAK, Bekir KOCAZEYBEK

Assessing E-Cadherin and Connexin 43 Gene Expressions in Colorectal Cancer

Saime SÜRMEN, Soykan ARIKAN, Özlem TİMİRCİ KAHRAMAN, Mustafa Gani SÜRMEN, Canan CACINA, İlhan YAYLIM

Preoperative Screening for COVID-19: Results from a Clinical Diagnostic Laboratory

Okan AYDOĞAN, Ezgi GÖZÜN ŞAYLAN, Özlem GÜVEN, Akif AYAZ, Türkan YİĞİTBAŞI

Cytotoxic and Cytostatic Effects of Targeting mTOR and Hedgehog Pathways in Acute Myeloid Leukemia

Enes ÇİÇEK, Fulya Mina KÜÇÜKTAŞ, Münevver YENİGÜL, Emel GENCER AKCOK

Germline Screening of Cancer-Related Genes in Turkish Ovarian Cancer Patients

Esra ARSLAN ATEŞ, Ceren ALAVANDA, Bilgen Bilge GEÇKİNLİ, İlter GÜNEY, Tuba GUNEL