|
Effect of Aspartam on histomorphometric alterations, kidney function and expression of Bcl2, Bax, Caspase 3, P53 Genes in Mice
|
Narges Zadsar1    , Hassan Morovvati 2, Zahra Tootian3 , Mohammadtaghi Sheybani4 , Mohammad Taheri5 , Hojat Anbara6 |
1- Ph.D Candidate in Comparative Anatomy and Embryology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
2- Professor, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. , hmorovvati@ut.ac.ir
3- Professor, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
4- Associate Professor, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
5- Expert of Dr. Rastegar Laboratories, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
6- Ph.D in Comparative Histology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. |
|
|
Abstract: (5318 Views) |
Background and Objective: Aspartame is a kind of artifical and non-sugar sweetener that is used as a sugar substitute in some foods and beverages. This study was done to determine effect of Aspartam on histomorphometric alterations, kidney function and expression of Bcl2, Bax, Caspase 3, P53 Genes in Mice.
Methods: In this experimental study, 36 adult male NMRI mice were allocated into four groups including control group and three experimental groups. The mice in the control group received 0.3 ml of distilled water by oral gavage for 90 days and the experimental groups received 40, 80 and 160 mg/kg aspartame, respectively orally and daily. One day after treatment, blood and kidney tissue samples were taken to evaluate biochemical, histomorphometric alterations and gene expression.
Results: Renal capsule diameter, glomerulus diameter and height of the epithelial layer of distal and proximal tubules were significantly reduced in treated groups compared to control group with increasing dosage of aspartame (P<0.05). However, the size of the urinary space and the diameter of the lumen of distal and proximal tubules were significantly increased in treated groups in compared to control group (P<0.05). The level of blood nitrogen urea (BUN) and creatinine significantly increased treated groups in compared to the control group with increasing dosage of aspartame (P<0.05). Also, with increasing dosage of aspartame, Bcl2 gene expression significantly reduced in treated groups in compared to the control group (P<0.05) however expression of Bax, Caspase 3 and p53 genes were significantly increased in treated groups compared to the control group (P<0.05).
Conclusion: Aspartame can cause changes in biochemical, histomorphometric indices, expression of Bcl2, Bax, Caspase 3 and P53 genes in mice kidney. |
|
Keywords: Aspartame [MeSH], Kidney [MeSH], Bcl2 Gene [MeSH], Bax , Caspase 3 [MeSH], P53 Gene [MeSH], Mice [MeSH]
Article ID: Vol23-03 |
|
|
Full-Text [PDF 1121 kb]
(10632 Downloads)
|
|
Type of Study: Original Articles |
Subject:
Physiology - Pharmacology
|
|
|
|
|
|
|
| References |
1. Magnason BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, et al. Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol. 2007; 37(8): 629-727. DOI: 10.1080/10408440701516184 [ DOI] [ PubMed] 2. Ager DJ, Pantaleone DP, Henderson SA, Katritzky AR, Prakash I, Walters DE. Cominercial, synthetic Non-nutritive sweeteners. The German Chemical Society. 1998 Agu; 37(13-14): 1802-17. DOI: 10.1002/(SICI)1521-3773(19980803)37:13/14<1802::AID-ANIE1802>3.0.CO;2-9 [ Article] [ DOI] 3. Nseir W, Nassar F, Assy N. Soft drinks consumption and nonalcoholic fatty liver disease. World J Gastroenterol. 2010 Jun; 16(21): 2579-88. DOI: 10.3748/wjg.v16.i21.2579 [ DOI] [ PubMed] 4. Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, Maza O, et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature. 2014 Oct; 514(7521): 181-86. DOI: 10.1038/nature13793 [ DOI] [ PubMed] 5. 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. DOI: 10.1023/a:1014419229301 [ DOI] [ PubMed] 6. Edmundson AB, Manion CV. Treatment of osteoarthritis with aspartame. Clin Pharmacol Ther. 1998 May; 63(5): 580-93. DOI: 10.1016/S0009-9236(98)90109-6 [ DOI] [ PubMed] 7. Pradhan S, Shah UH, Mathur AG, Sharma S. Aspartame: Sweetener with anti-inflammatory potential? J Pharmacol Pharmacother. 2010 Jul; 1(2): 113-14. DOI: 10.4103/0976-500X.72357 [ DOI] [ PubMed] 8. Sharma S, Jain NK, Kulkarni SK. Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs. Indian J Exp Biol. 2005 Jun; 43(6): 498-502. [ PubMed] 9. Christian B, McConnaghey K, Betchea E, Brantley S, Coffey A, Hammond L, et al. Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in rats. Pharmacol Biochem Behav. 2004 May; 78(1): 121-27. DOI: 10.1016/j.pbb.2004.02.017 [ DOI] [ PubMed] 10. Kim JY, Seo J, Cho KH. Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia. Food Chem Toxicol. 2011 Nov; 49(11): 2899-905. DOI: 10.1016/j.fct.2011.08.001 [ DOI] [ PubMed] 11. Hozayen WG, Soliman HAE, Desouky EM. Potential protective effects of rosemary extract, against aspartame toxicity in male rats. J Inter Acad Res Multidisc. 2014; 2(6): 111-25. [ Article] 12. Quadrilatero J, Bombardier E, Norris SM, Talanian JL, Palmer MS, Logan HM, et al. Prolonged moderate-intensity aerobic exercise does not alter apoptotic signaling and DNA fragmentation in human skeletal muscle. Am J Physiol Endocrinol Metab. 2010 Mar; 298(3): E534-47. DOI: 10.1152/ajpendo.00678.2009 [ DOI] [ PubMed] 13. Siu PM. Muscle apoptotic response to denervation, disuse, and aging. Med Sci Sports Exerc. 2009 Oct; 41(10): 1876-86. DOI: 10.1249/MSS.0b013e3181a6470b [ DOI] [ PubMed] 14. McMillan EM, Graham DA, Rush JWE, Quadrilatero J. Decreased DNA fragmentation and apoptotic signaling in soleus muscle of hypertensive rats following 6 weeks of treadmill training. J Appl Physiol (1985). 2012 Oct; 113(7): 1048-57. DOI: 10.1152/japplphysiol.00290.2012 [ DOI] [ PubMed] 15. Favaloro B, Allocati N, Graziano V, Di Ilio C, De Laurenzi V. Role of Apoptosis in disease. Aging (Albany NY). 2012 May; 4(5): 330-49. DOI: 10.18632/aging.100459 [ DOI] [ PubMed] 16. Westphal D, Dewson G, Czabotar PE, Kluck RM. Molecular biology of Bax and Bak activation and action. Biochim Biophys Acta. 2011 Apr; 1813(4): 521-31. DOI: 10.1016/j.bbamcr.2010.12.019 [ DOI] [ PubMed] 17. Qu D, Jiang M, Huang D, Zhang H, Feng L, Chen Y, et al. Synergistic Effects of The Enhancements to Mitochondrial ROS, p53 Activation and Apoptosis Generated by Aspartame and Potassium Sorbate in HepG2 Cells. Molecules. 2019 Jan; 24(3): 457. DOI: 10.3390/molecules24030457 [ DOI] [ PubMed] 18. Doss C, Olson KR. Antiseptics and disinfectants. In: Dart RC. Medical Toxicology. 3rd ed New York: Lippincott Williams & Wilkins. Chap 22. 2004; pp: 1246-99. 19. Onaolapo AY, Onaolapo OJ, Nwoha PU. Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice. Neurobiol Learn Mem. 2017 Mar; 139: 76-88. DOI: 10.1016/j.nlm.2016.12.021 [ DOI] [ PubMed] 20. Onaolapo AY, Abdusalam SZ, Onaolapo OJ. Silymarin attenuates aspartame-induced variation in mouse behaviour, cerebrocortical morphology and oxidative stress markers. Pathophysiology. 2017 Jun; 24(2): 51-62. DOI: 10.1016/j.pathophys.2017.01.002 [ DOI] [ PubMed] 21. Anbara H, Shahrooz R, Malekinejad H, Saadati S. [Protective Effects of Royal Jelly and Vitamin C against Experimental Hemolytic Anemia on Sex Hormones and Histochemical Testicle Tissue Histochemistry of Adult Mice]. J Shahid Sadoughi Uni Med Sci. 2016; 23(12): 1140-54. [Article in Persian] [ View at Publisher] 22. Tamatani M, Mitsuda N, Matsuzaki H, Okado H, Miyake S, Vitek MP, et al. A pathway of neuronal apoptosis induced by hypoxia/reoxygenation: roles of nuclear factor-kappaB and Bcl-2. J Neurochem. 2000 Aug; 75(2): 683-93. DOI: 10.1046/j.1471-4159.2000.0750683.x [ DOI] [ PubMed] 23. Harrison DC, Davis RP, Bond BC, Campbell CA, James MF, Parsons AA, et al. Caspase mRNA expression in a rat model of focal cerebral ischemia. Brain Res Mol Brain Res. 2001 Apr; 89(1-2): 133-46. DOI: 10.1016/s0169-328x(01)00058-4 [ DOI] [ PubMed] 24. Ashok I, Sheeladevi R. Biochemical responses and mitochondrial mediated activation of apoptosis on long-term effect of aspartame in rat brain. Redox Biol. 2014 Apr; 2: 820-31. DOI: 10.1016/j.redox.2014.04.011 [ DOI] [ PubMed] 25. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez López JA, et al. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci. 1998; 63(5): 337-49. DOI: 10.1016/s0024-3205(98)00282-3 [ DOI] [ PubMed] 26. Cheeseman KH. Mechanisms and effects of lipid peroxidation. Mol Aspects Med. 1993; 14(3): 191-97. DOI: 10.1016/0098-2997(93)90005-x [ DOI] [ PubMed] 27. Iman MM. Effect of aspartame on some oxidative stress parameters in liver and kidney of rats. Afr J Pharm Pharmacol. 2011 Jun; 5(6): 678-82. [ View at Publisher] 28. Sayed Saleh AA. Synergistic effect of N-acetyl cysteine and folic acid against aspartame- induced nephrotoxicity in rats. Int J of Adv Res. 2014 May; 2(5): 363-73. [ View at Publisher] 29. Tootian Z, Limouei H, Sheibani MT, Fazelipour S, SalarAmoli J. [Morphometrical and histometrical changes of kidney in immature mice exposed to aspartame]. 2013; 68(2): 159-65. DOI: 10.22059/jvr.2013.31963 [Article in Persian] [ View at Publisher] [ DOI] 30. Koçtürk S, Kayatekin BM, Resmi H, Açikgöz O, KaynakV, Ozer V. The apoptotic response to strenuous exercise of the gastrocnemius and solues muscle fibers in rats. Eur J Appl Physiol. 2008 Mar; 102(5): 515-24. DOI: 10.1007/s00421-007-0612-7 [ DOI] [ PubMed] 31. Ziaaldini MM, Koltai E, Csende Z, Goto S, Boldogh I, Taylor AW, et al. Exercise training increases anabolic and attenuates catabolic and apoptotic processes in aged skeletal muscle of male rats. Exp Gerontol. 2015 Jul; 67: 9-14. DOI: 10.1016/j.exger.2015.04.008 [ DOI] [ PubMed] 32. Dahabreh IJ, Schmid CH, Lau J, Varvarigou V, Murray S, Trikalinos TA. Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer. Am J Epidemiol. 2013 Jun; 177(12): 1317-25. DOI: 10.1093/aje/kws394 [ DOI] [ PubMed] 33. Xue X, Yu JL, Sun DQ, Kong F, Qu XJ, Zou W, et al. Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways. Asian Pac J Cancer Prev. 2014; 15(9): 3987-92. DOI: 10.7314/apjcp.2014.15.9.3987 [ DOI] [ PubMed] 34. Alsuhaibani ES. In vivo cytogenetic studies on aspartame. Comp Funct Genomics. 2010; 2010: 605921. DOI: 10.1155/2010/605921 [ DOI] [ PubMed] 35. Köhler C, Orrenius S, Zhivotovsky B. Evaluation of caspase activity in apoptotic cells. J Immunol Methods. 2002 Jul; 265(1-2): 97-110. DOI: 10.1016/s0022-1759(02)00073-x [ DOI] [ PubMed] |
|
| Send email to the article author |
|
|
|
Zadsar N, Morovvati H, Tootian Z, Sheybani M, Taheri M, Anbara H. Effect of Aspartam on histomorphometric alterations, kidney function and expression of Bcl2, Bax, Caspase 3, P53 Genes in Mice. J Gorgan Univ Med Sci 2021; 23 (1) :22-30 URL: http://goums.ac.ir/journal/article-1-3770-en.html
|
