AMELIORATIVE ROLE OF SILYMARIN AGAINST ASPARTAME–INDUCED BIOCHEMICAL CHANGES, OXIDATIVE STRESS, INFLAMMATORY EFFECT AND GENOTOXICITY IN MALE ALBINO RATS
DOI:
https://doi.org/10.22159/ijcpr.2020v12i1.36831Keywords:
Aspartame, Silymarin, Inflammatory marker, Oxidativeanti-oxidative status, Chromosomal aberrationsAbstract
Objective: Aspartame (ASP) is one of the most common artificial sweeteners. It has been recorded to be safe by World Health Organization. However, numerous publications have concluded that ASP is a genotoxic and carcinogenic sweetener.
Methods: The current study aims to examine the effect of ASP consumption (250 mg/kg body weight/day for 90 d) on some biochemical parameters, oxidative/antioxidative status in different tissues, Tumor Necrosis Factor-α (TNF-α), chromosomal aberration (CA) frequency and mitotic index (MI) percentage in addition to the possible ameliorative role of silymarin (50 mg/kg body weight/day for 90 d) against ASP-induced toxicity in male albino rats.
Results: The present results have confirmed that ASP is able to induce significant increase in the blood glucose level, liver, kidney and lipid function tests, Malondialdehyde (MDA) level, serum TNF-α level, frequency of CA and MI%. Meanwhile, Glutathione reduced level (GSH), Glutathione–S-transferase (GST) and catalase activity (CAT) were decreased by ASPadministration. Recovery group showed slight enhancement in all parameters but remained significant as compared to the control group. Co-administration of ASP with silymarin showed greater improvement than the recovery group.
Conclusion: Silymarin have an ameliorative role against biochemical oxidative stress, inflammatory changes in blood and different tissues, chromosomal aberrations and MI% induced by ASP administration.
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References
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3. Stegink LD. Aspartate and glutamate metabolism. In: Stegink LD, Filer Jr LJ. editors. Aspartame physiology and biochemistry. New York: Marcel Dekker; 1984. p. 47e-76.
4. Harper AE, Stegink LD, Filer LJJ. Phenylalanine metabolism. Newyork: Marcel Dekker; 1984. p. 77e109.
5. Opperman JA, Stegink LD, Filer LJ. Aspartame metabolism in animals. New York: Marcel Dekker; 1984. p. 141e59.
6. Butchko H. Aspartame review of safety. Regul Toxicol Pharmacol 2002;35:S1e93.
7. Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L. Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male swiss mice. Am J Ind Med 2010;53:1197–206.
8. Fagherazzi G, Vilier A, SaesSartorelli D, Lajous M, Balkau B, Clavel Chapelon F. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes. Am J Clin Nutr 2013;97:517–23.
9. Englund Ogge L, Brantsæter AL, Haugen M, Sengpiel V, Khatibi A, Myhre R, et al. Association between intake of artificially sweetened and sugar-sweetened beverages and preterm delivery: a large prospective cohort study. Am J Clin Nutr 2012;96:552–9.
10. Saleh AAS. Synergistic effect of N-acetyl cysteine and folic acid against aspartame-induced nephrotoxicity in rats. Int J Adv Res 2014;2:363–73.
11. El Haliem NGA, Mohamed DS. The effect of aspartame on the histological structure of the liver and renal cortex of adult male albinorat and the possible protective effect of pimpinellaanisum oil. Egypt J Histol 2011;34:715–26.
12. El Sakhawy M, Saeid S. Effect of long term administration of aspar-tame on the parotid salivary glands of male albino rats. Int J Adv Res 2014;2:850–85.
13. AbdElfatah AAM, Ghaly IS, Hanafy SM. Cytotoxic effect of aspartame (diet sweet) on the histological and genetic structures of female albino rats and their offspring. Pak J Biol Sci 2012;15:904-18.
14. Kren V, Walterova D. Silybin and silymarin-new effects and applications. Biomed 2005;149:29–41.
15. Kroll DJ, Shaw HS, Oberlies NH. Milk thistle nomenclature: why it mattersin cancer research and pharmacokinetic studies. Integr Cancer Ther 2007;6:110–9.
16. Hassani FV, Rezaee R, Sazegara H, Hashemzaei M, Shirani K. Effects of silymarin on neuropathic pain and formalin-induced nociception inmice. Iran J Basic Med Sci 2015;18:715–20.
17. WenWu J, Lin L, Tsai T. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 2009;121:185–93.
18. Fraschini F, Demartini G, Esposti D. Pharmacology of silymarin. Clin Drug Invest 2002;22:1.
19. Christian B, McConnaughey K, Bethea E, Brantley S, Coffey A. Chronic aspartame affects T-maze performance, brain cholinergic receptors and Na+,K+-ATPase in rats. Pharmacol Biochem Behav 2004;78:121–7.
20. Hjelle JJ, Dudley RE, Marietta MP, Sanders PG, Dickie BC. Plasma concentrations and pharmacokinetics of phenyl-alanine in rats and mice administered aspartame. Pharmacology 1992;44:48–60.
21. Thavasu PW, Longhurst S, Joel SP, Slevin ML, Balkwill FR. Measuring cytokine levels in blood. Importance of anticoagulants, processing and storage conditions. J Immunol Methods 1992;153:115-24.
22. Nasri H, Mortazavi M, Ghorbani A, Shahbazian H, Kheiri S. Oxford MEST classification in IgA nephropathy patients: a report from Iran. J Nephropathol 2012;1:31 42.
23. Trinder P. Determination of glucose in blood using glucose oxidase with an alternative oxygen receptor. Ann Clin Biochem 1969;6:24–7.
24. Patton C, Crouch R. Spectrophotometric and kinetics investigation of the berthelot reaction for the determination of ammonia. Anal Chem 1977;49:464-9.
25. Bartels H, Böhmer M, Heierli C. Serum creatinine determination without protein precipitation. Clin Chim Acta 1972;37:193-7.
26. Malloy HT, Evelyn KA. The determination of bilirubin with the photometric colorimeter. J Biol Chem 1937;119:481-90.
27. King J. The transaminases: alanine and aspartate transaminases. 15. In: Van D, editor. Practical clinical enzymology. London: Van D. Nostrand Co; 1965. p. 363-95.
28. King J. The hydrolases-acid and alkaline phosphatases. In: 16. Van D. editor. Practical clinical enzymology. London: Van D. Nostrand Co; 1965. p. 199-208.
29. Van Handel E, Zilversmit DB. Micro-method for direct 12. Determination of serum triglycerides. J Lab Clin Med 1957;50:152-7.
30. Allain CC, Poon LS, Chan CSG. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.
31. Ohkawa H, Ohishi W, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochemical 1979;95:351-8.
32. Beutler E, Duron O, Kelly MB. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-90.
33. Habig WH, MJbst MJ, Jakoby WB. Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.
34. Aebi H. [13] Catalase in vitro. Methodes Enzymol 1984;105:121-6.
35. Preston RJ, Dean BH, Galloway BJ, Holden S, McFee AF, Shelby M. Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells. Mutat Res 1987;189:157–65.
36. Levesque R. SPSS programming and data management: guide for SPSS and SAS. Users. 4th ed. SPSS Inc. Chicago. IL; 2007. p. 60606-6412.
37. Prokic MD, Paunovic MG, Matic MM, Djordjevic NZ, Ognjanovic MI. Effects of aspartame on biochemical and oxidative stress parameters in rat blood. Arch Biol Sci 2015;67:535-45.
38. Hassan MI. Low intake of aspartame induced weight gain and damage of brain and liver cells in weanling syrian hamsters. J Food Nutr Res 2016;4:152-6.
39. Appleton KM, Blundell JE. Habitual high and low consumers of artificially-sweetened beverages. Effects of sweet taste and energy on short-term appetite. Physiol Behav 2007;92:479-86.
40. Swithers SE, Davidson TL. A role for sweet taste. Calorie predictive relations in energy regulation by rats. Behav Neurosci 2008;122:61-173.
41. Leibowitz SF. Neurochemical systems of the hypothalamus-control of feeding and drinking behaviour and water-electrolyte excretion. In: Handbook of the Hypothalamus. Eds. PJ Morgane, J Panksepp; 1980. p. 299-343.
42. 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 2001;75:41-7.
43. Caro JF, Sinha MK, Kolaczynski JW, Zhang PL, Considine RV. Leptin the tale of an obesity gene. Diabetes 1996;45:1455-62.
44. Humphries P, Pretorius E, Naud EH. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr 2008;62:451-62.
45. Omar SMM. Effect of aspartame on the frontal cortex of adult male albino rats. a light and electron microscopic study. Egypt J Histol 2009;32:346–57.
46. Azeez O, Alkass S. Effect of long-term consumption of aspartame on body weight, blood glucose, lipid profile, kidney and liver functions in rats. Int J Curr Adv Res 2018;7:14464-74.
47. Ferland A, Brassard P, Poirier P. Is aspartame really safer in reducing the risk of hypoglycemia during exercise in patients with type 2 diabetes? Diabetes Care 2007;30:e59.
48. Nuttall FQ, Schweim KJ, Gannon MC. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res 2006;38:518–23.
49. Finamor IA, Ourique GM, Pes TS, Saccol EMH, Bressan CA. The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats. Neurochem Res 2014;39:1681–90.
50. Bouhalit S, Kechrid Z. Protective effect of silymarin extracted from silybummarianum seeds upon nickel-induced hepatotoxicity in albino wistar rats. Ann Microbiol Immunol 2018;1:1-5.
51. Cheng J, Xiao L. The application of silymarin to hepatitis fibrosis. Int J Diges Dis 2007;27:69-71.
52. Iyaswamy A, Wankhar D, Loganathan S, Shanmugam S, Rajan R. Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate-deficient rat model. J Nutr Intermediary Metabol 2017;8:41-50.
53. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci 1998;63:337-49.
54. Gafar HB, Taha N, Noeman SN, Mandour A, Lepda M. Protective role of alpha-lipoic acid against the deleterious effects of both natural and artificial sweetener (Sucrose and Aspartame) in albino rats. Alex J Vet Sci 2016;49:105-15.
55. El-Sawy AF, El-Maddawy ZKH, Ashoura NR. Role of silymarin in restoring the deleterious effects induced by dexamethasone in male rats. AJVS 2018;59:125-35.
56. Shelbaya LA. Evaluation of the protective and antioxidant activity of milkthistle on paracetamol-induced toxicity in rats. J Am Sci 2013;9:272-8.
57. Waggas A, Soliman K, Moubarz G, Abd Elfatah A, Taha M. Potential protective effects of aqueous extract of majoram leaves, against aspartame induced renal toxicity in female rats. American-Eurasian J Toxicol Sci 2015;7:267-78.
58. Bahr I, Zaki M. Renal genomic instability induced by aspartame and the possible influence of the flaxseed oil and coenzyme Q10 in male rats. Life Sci J 2014;11:301-8.
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Published
15-01-2020
How to Cite
ELBALLAT, S. E., and A.-S. M. ABAS. “AMELIORATIVE ROLE OF SILYMARIN AGAINST ASPARTAME–INDUCED BIOCHEMICAL CHANGES, OXIDATIVE STRESS, INFLAMMATORY EFFECT AND GENOTOXICITY IN MALE ALBINO RATS”. International Journal of Current Pharmaceutical Research, vol. 12, no. 1, Jan. 2020, pp. 41-55, doi:10.22159/ijcpr.2020v12i1.36831.
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