The Effect of Long-term Exposure to Aspartame on Histomorphology, Histomorphometry, Histochemistry and Expression of Caspase-3 Gene in the Small Intestine of Mice

Document Type : Original Article(s)

Authors

1 PhD Candidate, Department of Comparative Histology and Embryology, School of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Professor, Department of Comparative Histology and Embryology, School of Veterinary Medicine, University of Tehran, Tehran, Iran

3 PhD, Department of Comparative Histology and Embryology, School of Veterinary Medicine, University of Tehran, Tehran, Iran

Abstract

Background: Aspartame is a member of the artificial sweetener family, which is increasingly used in diet products, low-calorie foods, and various types of foods, medications, and hygiene products. The present study was conducted to evaluate the effects of aspartame on the small intestine of mice.
Methods: In this experimental study, 36 adult male mice were randomly divided into four groups of nine each. Three groups received aspartame orally via gavage at doses of 40, 80, and 160 mg/kg.BW, respectively, for 90 days. Additionally, a control group was included. 24 hours after the last treatment, serum, and tissue samples were collected for biochemical, histomorphological, histomorphometrical, histochemical, and gene expression analyses.
Findings: Significant changes in carbohydrate compositions were not observed in the histochemical studies between the groups, but the amount of fibrous tissue increased in the groups receiving aspartame. In histomorphometric evaluations of the small intestine, aspartame at doses of 80 and 160 mg/kg. BW caused a significant reduction in histomorphometrical parameters compared to the control group. Aspartame administration dose-dependently led to significant changes in oxidative parameters compared to the control group. Additionally, the expression of the Caspase-3 gene showed a significant increase in the group receiving aspartame at a dose of 160 mg/kg. BW compared to the control group.
Conclusion: It seems that aspartame can cause negative effects on histomorphology, histomorphometry, histochemistry, and oxidative parameters in a dose-dependent manner and increases the expression of the Caspase-3 gene in the small intestine.

Highlights

Seyed Ehsan Rahmani: Google Scholar

Hassan Morovvati: Google Scholar

Hojat Anbara: Google Scholar

Keywords

Main Subjects

References

  1. Sheibani MT, Anbara H, Morovvati H, Razi M, SalarAmoli J. Effect of long term-administration of aspartame on sperm quality, testosterone and oxidant parameters in mice [in Persian]. J Ilam Univ Med Sci 2019; 27(3): 150-61.
  2. Anbara H, Sheibani MT, Razi M. Long-term effect of aspartame on male reproductive system: evidence for testicular histomorphometrics, Hsp70-2 protein expression and biochemical status. Int J Fertil Steril 2020; 14(2): 91-101.
  3. Anbara H, Sheibani MT, Razi M, Kian M. Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model. Environ Toxicol 2021; 36(2): 223-37.
  4. Tobey NA, Heizer WD. Intestinal hydrolysis of aspartylphenylalanine--the metabolic product of aspartame. Gastroenterology 1986; 91(4): 931-7.
  5. Hosseini M, Morovvati H, Anbara H. The effect of long-term exposure to aspartame on histomorphometric, histochemical and expression of P53, Bcl-2 and Caspase-3 genes in the ovaries of mice [in Persian]. Qom Univ Med Sci J 2021; 15(6): 414-25.
  6. Anbara H, Kian M, Darya GH, Sheibani MT. Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53-dependent apoptosis in a mouse model. Int J Exp Pathol 2022; 103(6): 252-62.
  7. Onaolapo AY, Onaolapo OJ, Nwoha PU. Alterations in behaviour, cerebral cortical morphology and cerebral oxidative stress markers following aspartame ingestion. J Chem Neuroanat 2016; 78: 42-56.
  8. Anbara H, Shalizar Jalali A, Shahrooz R, Razi M. Protective effect of royal jelly against phenylhydrazine-induced histological injuries of small intestine of mice: morphometric analyses [in Persian]. Qom Univ Med Sci J 2016; 9(11): 12-21.
  9. Oyama Y, Sakai H, Arata T, Okano Y, Akaike N, Sakai K, et al. Cytotoxic effects of methanol, formaldehyde, and formate on dissociated rat thymocytes: a possibility of aspartame toxicity. Cell Biol Toxicol 2002; 18(1): 43-50.
  10. Morovvati H, Koohi MK, Khaksar Z, Morshedi F, Anbara H, Parsaei F, et al. Histological and histometrical study of prostate following administration of sertraline in adult mice. Iran South Med J 2020; 23(3): 205-221.
  11. Beck B, Burlet A, Max JP, Stricker-Krongrad A. Effects of long-term ingestion of aspartame on hypothalamic neuropeptide Y, plasma leptin and body weight gain and composition. Physiol Behav 2002; 75(1-2): 41-7.
  12. Leme FAGdL, Azoubel R. Effects of aspartame on exocrine pancreas of rat fetuses. Int J Morphol 2006; 24(4): 679-84.
  13. Gul SS, Hamilton ARL, Munoz AR, Phupitakphol T, Liu W, Hyoju SK, et al. Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice. Appl Physiol Nutr Metab 2017; 42(1): 77-83.
  14. Yang Q. Gain weight by "going diet?" Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. Yale J Biol Med 2010; 83(2): 101-8.
  15. Ashok I, Sheeladevi R, Wankhar D. Long term effect of aspartame (Artificial sweetener) on membrane homeostatic imbalance and histopathology in the rat brain. Free Radicals and Antioxidants 2013; 3(Suppl): S42-S49.
  16. Hooshmand Abbasi R, Tootian Z, Sheibani MT, Fazelipour S, Limouei H. Histological and histometrical study of duodenum in mice after ingestion of Aspartame [in Persian]. Journal of Veterinary Research 2016; 71(2): 205-10.
  17. Chiedozie MC, Donatus EG, Amoo-Tella SY, Enang UAI. Moringa oleifera seed actions following aspartame consumption: a systematic evaluation of the large intestine. Sch Int J Anat Physiol 2022; 5(1): 15-24.
  18. Shil A, Chichger H. Artificial sweeteners negatively regulate pathogenic characteristics of two model gut bacteria, Coli and E. Faecalis. Int J Mol Sci 2021; 22(10): 5228.
  19. Morovvati H, Anbara H, Sheibani M, Koohi M, Hasanzadeh A. The effect of long-term exposure to aspartame on histomorphometric and histochemical adrenal gland in adult NMRI Mice [in Persian]. Armaghan-e-Danesh 2019; 24(2): 150-69.
  20. Anbara H, Shahrooz R, Shalizar Jalali A, Razi M, Kalantari Hesari A. Protective effect of vitamin C against hemolytic anemia-induced changes in small intestine histoarchitecture of phenylhydrazine-treated mice [in Persian]. J Shahrekord Uuniv Med Sci 2015; 17(4): 70-9.
  21. Anbara H, Shahrooz R, Mozafari AA, Malekinejad H, Morovvati H, Sheybani MT, et al. Protective Effects of Ethyl Pyruvate and Vitamin E Against Phenylhydrazine-Induced Nephrotoxicity in Mice [in Persian]. Yafte 2018; 20(1): 52-67.
Journal of Isfahan Medical School
Volume 41, Issue 738
2nd Week, December
November and December 2023
Pages 884-895

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History

  • Receive Date: 23 September 2023
  • Accept Date: 20 November 2023

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