Research Article | Volume: 4, Issue: 2, March-April, 2016

Alterations in antioxidant defense system in hepatic and renal tissues of rats following aspartame intake

Saeed A. Alwaleedi   

Open Access   

Published:  Apr 21, 2016

DOI: 10.7324/JABB.2016.40207

Aspartame is one of the most common artificial sweeteners in use today worldwide. Aspartame has been implicated in many health problems. The study aimed to investigate whether aspartame consumption induces oxidative stress and whether it can threaten the antioxidant defense system in hepatic and renal tissues. The experiment was performed on adult male albino rats. They were distributed into 4 groups, group I represented the control animals and received orally water. The rest were given aspartame in a dose 50 mg/kg for 15, 30 and 60 days respectively. Blood was collected and centrifuged to obtain serum for the determination of serum enzymes. The tissue samples were homogenized, centrifuged and the clear supernatant was collected for further biochemical analysis. The results showed a significant increase in LPO level in liver and kidney. A remarkable reduction in GSH content was also observed in both hepatic and renal tissues. The activities of antioxidant enzymes SOD, CAT, GPx and GR were significantly reduced in both liver and kidney. In addition, the results also indicated a significant increase in activities of serum marker enzymes ALT, AST, ALP and GGT. The data provided in this study clearly point out that aspartame consumption at a dose of 50 mg/kg induces oxidative stress in hepatic and renal tissues by generation of free radicals.

Keyword:     Aspartameoxidative stressantioxidantfree radicalsliverkidney.


Saeed A. Alwaleedi. Alterations in antioxidant defense system in hepatic and renal tissues of rats following aspartame intake. J App Biol Biotech. 2016; 4 (02): 046-052. DOI: 10.7324/JABB.2016.40207

Copyright: Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike license.

HTML Full Text


1. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer PS, Waddell WJ, Walker R, Williams GM. Aspartame: a safety elevation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol. 2007; 37:629-727.

2. Rencuzogullari E, Tuylu BA, Topaktas M, Ila HB, Kayraldiz A, Arslan M, Diler SB. Genotoxicity of aspartame. Drug Chem Toxicol. 2004; 27:257–268.

3. Oppermann JA. Aspartame metabolism in animals. In: Stegink LD, Filer LJ (ed). Aspartame, physiology and biochemistry. Marcel Dekker Inc, New York; 1984, pp 141-159.

4. Stegink LD. Aspartame metabolism in humans: acute dosing studies. In: Stegink L, Filer L (ed) Aspartame: Physiology and biochemistry. Marcel Dekker, New York; 1984, pp 509-553.

5. Trocho C, Pardo R, Rafecas I, Virgili J, Remesar X, Fernandez- Lopez JA, Alemany M. Formaldehyde derived from dietary aspartame binds to tissue components in vivo. Life Sci. 1998; 63:337-349.

6. Woodrow C. Monte and methanol. J Appl Nutr. 1984; 36:1-15.

7. Maher TJ and Wurtman RJ. Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspect. 1987; 75:53-57.

8. Dailey JW, Lasley SM, Burger RL, Bettendorf AF, Mishra PK and Jobe PC. Amino acids, monoamines and audiogenic seizures in genetically epilepsy-prone rats: effects of aspartame. Epilepsy Res. 1991; 8:122-133.

9. Diomede L, Romano M, Guiso G, Caccia S, Nava S, Salmona M. Interspecies and interstrain studies on the increased susceptibility to metrazol-induced convulsions in animals given aspartame. Food Chem Toxicol. 1991; 29:101-106.

10. Humphries P, Pretorius E, Naude H. Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr. 2008; 62:451-462.

11. Kruse JA. Methanol poisoning. Intensive Care Med. 1992; 18:391-397.

12. Davoli E. Serum methanol concentrations in rats and in men after a single dose of aspartame. Food Chem Toxicol. 1986; 24:187-189.

13. Poli G. Liver damage due to free radicals. Br Med Bull. 1993; 49:604-609.

14. Parthasarathy JN, Ramasundaram SK, Sundaramahalingam M, Pathinasamy SD. Methanol induced oxidative stress in rat lymphoid organs. J Occup Health. 2006; 48:20-27.

15. Castro GD, Costantini MH, Delgado de layno AM, Castro A. Rat liver microsomal and nuclear activation of methanol to hydroxyl methyl free radicals. Toxicol Lett. 2002; 129:227-236.

16. Ishak KG, Zimmerman HJ, Ray MB. Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. Alcohol Clin Exp Res. 1991; 15:45-66.

17. Fernandez-Checa JC, Kaplowitz N, Colell A, Garcia-Ruiz C. Oxidative stress and alcoholic liver disease. Alcohol Health Res World. 1997; 21:321-324.

18. Betteridge DJ. What is oxidative stress. Metabolism. 2000; 49:3-4.

19. Lopaczyski W, Zeisel SH. Antioxidants, programmed cell death, and cancer. Nutr Res. 2001; 21:295-307.

20. Karim A, Burns T. Metabolism and pharmacokinetics of radio labeled aspartame in normal subjects. In: Tschanz C, Butchko HH, Stargel WW, Kotsonis FN(ed) The clinical evaluation of a food additive. Assessment of aspartame. Boca Raton, New York, London, Tokyo: CRC; 1996, pp 57-66.

21. Stegink LD, Filer LJ. Effects of aspartame ingestion on plasma aspartate, phenylalanine and methanol concentrations in normal adults. In: Tschanz C, Butchko HH, Stargel WW, Kotsonis FN (ed) The clinical evaluation of a food additive. Assessment of aspartame. Boca Raton, New York, London, Tokyo: CRC Press; 1996, pp 67-86.

22. Trefz FK, Bickel H. Tolerance in PKU heterozygotes. In: Tschanz C, Butchko HH, Starge, WW, Kotsonis FN (ed) The clinical evaluation of a food additive. Assessment of aspartame; 1996, pp. 149-160.

23. Stegink LD. The aspartame story: a model for the clinical testing of a food additive. Am J Clin Nutr. 1987; 46:204-215.

24. Cheese-man KH. Mechanisms and effects of lipid peroxidation. Mol Aspects Med. 1993; 14:191-197.

25. Mylonas C and Kouretas D. Lipid peroxidation and tissue damage. In vivo. 1999; 13:295-309.

26. Bergendi L, Benes L, Durackova Z, Ferencik. Chemistry, Physiology and Pathology of free radicals. Life Sci. 1999; 65:1865-1874.

27. Zeyuan D, Bingyin T, Xiaolin L, Jinming H, Yifeng C. Effect of green tea and black tea on the blood glucose, the blood triglycerides and antioxidation in aged rats. J Agric Food Chem. 1998; 46:3875-3878.

28. Zararsiz I, Sarsilmaz M, Tas U, Kus I, Meydan S, Ozan E. Protective effect of melatonin against formaldehyde- induced kidney damage in rats. Toxicol Ind Health. 2007; 23:573-579.

29. Winterbourn CC. Concerted antioxidant activity of glutathione and superoxide dismutase. In: Packer L, Fuchs J (ed) Biothiols in health and disease. Marcel Dekker Inc, New York; 1995, pp 117-34.

30. Abuja PM, Albertini R. Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins. Clin Chim Acta. 2001; 306:1-17.

31. Singh P, Mann KA, Mangat HK, Kaur G. Prolonged glutamate excitotoxicity: Effects of mitochondrial antioxidants and antioxidant enzymes. Mol Cell Biochem. 2003; 243:139-145.

32. Hashimoto K, Takasaki W, Yamoto T, Manabe SI, Tsuda S. Effect of glutathione (GSH) depletion on DNA damage and blood chemistry in aged and young rats. J Toxicol Sci. 2008; 33:421-429.

33. Jones DJ, Eklow L, Thor H, Orrenius S. Metabolism of hydrogen peroxide in isolated hepatocytes: relative contribution of catalase and glutathione peroxidase in decomposition of endogenous generated H2O2. Arch Biochem Biophys. 1981; 210:505-516.

34. Meister A, Anderson S. Glutathione . Ann Rev Biochem. 1983; 52: 711-760.

35. Oyama Y, Sakai H, Arata T, Okano Y, Akaike N, Sakai K, Noda K. Cytotoxic effects of methanol, formaldehyde and formate on dissociated rat thymocytes: a possibility of aspartame toxicity. Cell Biol Toxicol. 2002; 18:43-50.

36. Pankow D, Jagielki S. Effect of methanol on modifications of hepatic glutathione concentration on the metabolism of dichloromethane to carbon monoxide in rats. Hum Exp Toxicol. 1993; 12:227-231.

37. Sogut, S, Songur A, Ozen OA, Ozyurt H, Sarsilmaz M. Does the sub acute (4 week) exposure to formaldehyde inhalation lead to oxidant/antioxidant imbalance in rat liver. Eur J Gen Med. 2004 1:26-32.

38. Skrzydlewska E. Toxicological and metabolic consequences of methanol poisoning. Toxicol Mechan Methods. 2003; 13:277-293.

39. Prabhakar R, Vreven T, Morokuma K, Musaev DG. Elucidation of the mechanism of selenoprotein glutathione peroxidase (GPx) catalyzed hydrogen peroxide reduction by two glutathione molecules: a density functional study. Biochemistry. 2005; 44:11864-11871.

40. Reiter RJ. Melatonin: lowering the high price of free radicals. News Physiol Sci. 2000; 15:246-250.

41. Morena I, Pichardo S, Jos A, Gomez-Amores L, Mate A, Vasquez CM, Camean AM. Antioxidant enzyme activities and lipid peroxidation in liver and kidney of rats exposed to Microcystin LR administered intraperitoneally. Toxicon. 2005; 45:395-402.

42. Fridovich I. Superoxide dismutase. Ann Rev Biochem. 1975; 44:147-159.

43. Kono Y, Fridorich I. Superoxide radical inhibits catalase. J Biol Chem. 1982; 257:5751-5754.

44. Pigeolet E, Corbisler P, Houbion A. Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev. 1990; 51:283-97.

45. Skrzydlewska E, Elas M, Farbiszewski R, Roszkowska A. Effect of methanol intoxication on free-radical induced protein oxidation. J Appl Toxicol. 2000; 20:239-243.

46. Gulec M, Gurel A, Armutcu F. Vitamin E protects against oxidative damage caused by a formaldehyde in the liver and plasma of rats. Mol Cell Biochem. 2006; 290:61-67.

47. Chang JR, Xu DQ. Effects of formaldehyde on the activity of superoxide dismutase and glutathione peroxidase and the concentration of malondialdehyde. Wei Sheng Yan Jiu Sept. 2006; 35:653- 655.

48. Tuna G, Erkmen GK, Dalmizrak O, Dogan A, Ogus IH, Ozer N. Inhibition characteristics of hypericin on rat small intestine glutathione- S- transferase. Chem Biol Interact. 2010; 188:59-65.

49. Mourad IM. Effect of aspartame on some oxidative stress parameters in liver and kidney of rats. Afr J Pharm Pharmacol. 2011; 5:678-682.

50. Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians. CMAJ. 2005; 172:367-379.

51. Lee DH, Blomhoff R, Jacobs DR. Serum gamma glutamyl transferase a marker of oxidative stress. Free Radical Res. 2004; 38:535-539.

Article Metrics

176 Absract views 160 PDF Downloads 336 Total views

Related Search

By author names

Citiaion Alert By Google Scholar

Name Required
Email Required Invalid Email Address

Comment required
Similar Articles