The effect of aspartame on rat brain xenobiotic-metabolizing enzymes

Human and Experimental Toxicology

Volumn 25, Issue 8, 2006, Pages 453-459

  Vences Mejia A ^a   Labra Ruiz N ^a   Hernandez Martinez N ^a   Dorado Gonzalez V ^a   Gomez Garduno J ^a   Perez Lopez I ^a   Nosti Palacios, R ^a   Carranza, R Camacho ^b   Espinosa Aguirre, J J ^b  

^a INSTITUTO NACIONAL DE PEDIATRÍA   (Mexico)

^b UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

Author keywords

Aspartame; Brain; Cytochrome P450; Enzyme induction

Indexed keywords

4 NITROPHENOL HYDROXYLASE; ASPARTAME; CYTOCHROME P450; CYTOCHROME P450 1A1; CYTOCHROME P450 2B1; CYTOCHROME P450 2B2; CYTOCHROME P450 3A; OXYGENASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN; ENZYME ACTIVITY; ENZYME INDUCTION; MALE; MEDICAL RESEARCH; NONHUMAN; PRIORITY JOURNAL; RAT; XENOBIOTIC METABOLISM;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; ASPARTAME; BRAIN; MALE; MICROSOMES; RATS; RATS, WISTAR; XENOBIOTICS;

ANIMALIA; RATTUS NORVEGICUS;

EID: 33748651220     PISSN: 09603271     EISSN: None     Source Type: Journal    
DOI: 10.1191/0960327106het646oa     Document Type: Article

References (41)

1. Meyer H. Aspartame as part of the solution. Food Sci Technol 2005; 19: 43-45.
2. Gougeon R, Spidel M, Lee K, Field CJ. Canadian diabetes association national nutrition committee technical review: Non-nutritive intense sweeteners in diabetes management. Can J Diabetes 2004; 128: 385-99.
3. Halimi S. Diabetes in 2005. Nephrologie et Therapeutique 2006; 2: S2-7.
4. Maher TJ, Wurtman RJ. Possible neurologic effects of aspartame, a widely used food additive. Environ Health Perspectives 1987; 75: 53-57.
5. Pinto JMB, Majer TJ. Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice. Neuropharmacology 1988; 27: 51-55.
6. Yokogoshi H, Roberts CH, Caballero B, Wurtman RJ. Effects of aspartame and glucose administration on brain and plasma levels of large neutral amino acids and brain 5-hydroxyindioles. Am J Clin Nutr 1984; 40: 1-7.
7. Krebs MO. Excitatory amino acids: a new class of neurotransmitters: pharmacology and functional properties. Encephale 1992; 18: 271-79.
8. Milner JD, Wurtman RJ. Tyrosine availability: a presynaptic factor controlling catecholamine release. Adv Exp Med Biol 1987; 221: 211-21.
9. Tilson HA, Hong JS, Sobotka TJ. High doses of aspartame have no effects on sensorimotor function or learning and memory in rats. Neurotoxicol Teratol 1991; 13: 27-35.
10. Shaywitz BA, Sullivan CM, Anderson GM, Gillespie SM, Sullivan B, Shaywits SE. Aspartame, behaviour, and cognitive function in children with attention deficit disorder. Pediatrics 1994; 93: 70-75.
11. Spiers PA, Sabounjian L, Reiner A, Myers DK, Wurtman J, Schomer DL. Aspartame: neuropsychologic and neurophysiologic evaluation of acute and chronic effects. Am J Clin Nutr 1998; 68: 531-37.
12. Potts WJ, Bloss JL, Nutting EF. Biological properties of aspartame: I. Evaluation of central nervous system effects. J Environ Pathol Toxicol 1980; 3: 341-53.
13. Dow-Edwards DL, Scribani LA, Riley EP. Impaired performance on odor-aversion testing following prenatal aspartame exposure in the guinea pig. Neurotoxicol Teratol 1989; 11: 413-16.
14. +-ATPase in rats. Pharmacol Biochem Behav 2004; 78: 121-27.
15. Guengerich FP, Shimada T. Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem Res Toxicol 1991; 4: 391-407.
16. Guengerich FP. Influence of nutrients and other dietary materials on cytochrome P450 enzymes. J Clin Nutr 1995; 61: 651S-58S.
17. Ravindranath V. Metabolism of xenobiotics in the central nervous system. Implications and changes. Biochem Pharmacol 1998; 56: 547-51.
18. Pelkonen O, Raunnio H. Metabolic activation of toxins: tissue-specific expression and metabolism in target organs. Environ Health Perspect 1997; 105: 767-74.
19. Tutelyan VA, Kravchenko LV, Kuzmina EE. The effect of aspartame on the rat activity of rat liver xenobiotic-metabolizing enzymes. Drug Metab Dispos 1990; 18: 223-25.
20. Maron DM and Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res 1983; 113: 173-215.
21. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265-75.
22. Burke MD, Thompson S, Elcombe CR, Halpert J, Haaparanta T, Mayer RT. Ethoxy-, penthoxy-, and benxyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P450. Biochem Pharmacol 1985; 34; 3337-45.
23. Burke MD, Thompson S, Weaver RJ, Wolf CR, Mayer RT. Cytochrome P450 specificities of alkoxyresorufin O-dealkylation in human and rat liver. Biochem Pharmacol 1994; 48: 923-36.
24. Koop DR. Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P450 isozyme 3a. Mol Pharmacol 1986; 29: 399-404.
25. Alexidis AN, Commandeur JN, Rekka EA. Novel piperidine derivatives: inhibitory properties towards cytochrome P450 isoforms and cytoprotective and cytotoxic characteristics, Environ Toxicol Pharmacol 1996; 1: 81-88.
26. Laemmli UK. Maturation of the head of bacteriophage T4 I DNA packaging events. Nature 1970; 227: 680-85.
27. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350-54.
28. Ranney RE, Oppermann JA. A review of the metabolism of the aspartyl moiety of aspartame in experimental animals and man. J Environ Pathol Toxicol 1979; 2: 979-85.
29. Burgert SL, Andersen DW, Stegink LD, Takeuchi H, Schedl HP. Metabolism of aspartame and its L-phenylalanine methyl ester decomposition product by porcine gut. Metabolism 1991; 40: 612-18.
30. Gram TE, Okine LR, Gram RA. The metabolism of xenobiotics by certain extrahepatic organs and its relation to toxicity. Annu Rev Pharmacol Toxicol 1986; 26: 259-91.
31. Fernstrom JD. Oral aspartame and plasma phenylalanine: pharmacokinetic difference between rodents and man, and relevance to CNS effects of phenylalanine. J Neural Transm 1989; 75: 159-64.
32. FDA (Food and Drug Administration). Food additives permitted for direct addition to food for human consumption; aspartame. Fed Regist 1996; 61: 33654-56.
33. Health Protection Branch. Information letter: aspartame. Health and Welfare Canada, 1987.
34. Molinary V. Preclinical studies of aspartame in non primate animals. In Stegink LD, Filer LJ Jr eds. Aspartame, physiology and biochemistry. Marcel Dekker, Inc., 1984: 289-306.
35. Gervasini G, Carrillo JA, Benitez J. Potential role of cerebral cytochrome P450 in clinical pharmacokinetics. Modulation by endogenous compounds. Clin Pharmacokinet 2004; 43: 693-706.
36. Miksys S, Hoffmann E, Tyndale RF. Regional and cellular induction of nicotine-metabolizing CYP2B1 in rat brain by chronic nicotine treatment. Biochem Pharmacol 2000; 59: 1501-11.
37. Oppermann JA. Aspartame metabolism in animals. In Stegink LD, Filer LJ Jr eds. Aspartame, physiology and biochemistry. Marcel Dekker, Inc., 1984: 141-59.
38. Roak-Foltz R, Leveille GA. Projected aspartame intake: daily ingestion of aspartic acid, phenylalanine, and methanol. In Stegink LD, Filer LJ Jr eds. Aspartame, Physiology and Biochemistry. Marcel Dekker, Inc., 1984: 201-205.
39. Doita HK, Simanowsky UA. In Hathcock JN ed. Nutritional Toxicology. Academic Press, 1987.
40. Allis JW, Brown BL, Simmons JE, Hatch AM, House DE. Methanol potentiation of carbon tetrachloride hepatotoxicity: the central role of cytochrome P450. Toxicology 1996; 112: 131-40.
41. Soffritti M, Belpoggi F, Esposti DD, Lambertini L. Aspartame induces lymphomas and leukaemias in rats. Eur J Oncol 2005; 10: 107-16.