This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Vences-Mejía, A Articles by Espinosa-Aguirre, J. Search for Related Content PubMed PubMed Citation Articles by Vences-Mejía, A Articles by Espinosa-Aguirre, J. Social Bookmarking                   What's this?

The Effect of Aspartame on Rat Brain Xenobiotic-Metabolizing Enzymes

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

N Labra-Ruíz

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

N Hernández-Martínez

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

V Dorado-González

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

J Gómez-Garduño

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

I Pérez-López

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

R Nosti-Palacios

Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur, 3700-C, 04530 México, D.F., México

R Camacho Carranza

Instituto de Investigaciones Biomédicas, UNAM, Apartado postal 70228, Ciudad Universitaria 04510 México, D.F., México

JJ Espinosa-Aguirre

Instituto de Investigaciones Biomédicas, UNAM, Apartado postal 70228, Ciudad Universitaria 04510 México, D.F., México

This study demonstrates that chronic aspartame (ASP) consumption leads to an increase of phase I metabolizing enzymes (cytochrome P450 (CYP)) in rat brain. Wistar rats were treated by gavage with ASP at daily doses of 75 and 125 mg/kg body weight for 30 days. Cerebrum and cerebellum were used to obtain microsomal fractions to analyse activity and protein levels of seven cytochrome P450 enzymes. Increases in activity were consistently found with the 75 mg/kg dose both in cerebrum and cerebellum for all seven enzymes, although not at the same levels: CYP 2E1-associated 4-nitrophenol hydroxylase (4-NPH) activity was increased 1.5-fold in cerebrum and 25-fold in cerebellum; likewise, CYP2B1-associated penthoxyresorufin O-dealkylase (PROD) activity increased 2.9- and 1.7-fold respectively, CYP2B2-associated benzyloxyresorufin O-dealkylase (BROD) 4.5- and 1.1- fold, CYP3A-associated erythromycin N-demethylase (END) 1.4- and 3.3-fold, CYP1A1-associated ethoxyresorufin O-deethylase (EROD) 5.5- and 2.8-fold, and CYP1A2- associated methoxyresorufin O-demethylase (MROD) 3.7- and 1.3-fold. Furthermore, the pattern of induction of CYP immunoreactive proteins by ASP paralleled that of 4-NHP-, PROD-, BROD-, END-, EROD- and MROD-related activities only in the cerebellum. Conversely, no differences in CYP concentration and activity were detected in hepatic microsomes of treated animals with respect to the controls, suggesting a brain-specific response to ASP treatment.

Key Words: aspartame • brain • cytochrome P450 • enzyme induction

Human & Experimental Toxicology, Vol. 25, No. 8, 453-459 (2006)
DOI: 10.1191/0960327106het646oa


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?