The Effect of Aspartame on Rat Brain Xenobiotic-Metabolizing Enzymes

Abstract

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.