l-Cysteine and glutathione restore the modulation of rat frontal cortex Na+, K+ -ATPase activity induced by aspartame metabolites.
BACKGROUND
Studies have suggested that aspartame (ASP) ingestion is implicated in neurological problems.


OBJECTIVE
The aim of this study was to evaluate rat frontal cortex Na+, K+ -ATPase and Mg2+ -ATPase activities after incubation with ASP or each of its metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately.


METHODS
Suckling rat frontal cortex homogenates or pure Na+, K+ -ATPase were incubated with ASP metabolites. Na+, K+ -ATPase and Mg2+ -ATPase activities were measured spectrophotometrically.


RESULTS
Incubation of frontal cortex homogenate or pure Na+, K+ -ATPase with various ASP concentrations as expected in the cerebrospinal fluid (CSF) after ASP consumption of 34, 150 or 200mg/kg, decreased the frontal cortex enzyme activity by 33%, 53% or 57%, respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation of frontal cortex homogenate with each one of the expected ASP metabolites in the CSF, except MeOH, which are related to the intake of the above mentioned doses of the sweetener, resulted in an activation of the membrane Na+, K+ -ATPase, as well as pure enzyme. Frontal cortex Mg2+-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) to ASP metabolites mixtures, corresponding to 150 or 200mg/kg doses of the sweetener, completely or partially restored to normal the modulated membrane and pure Na+, K+ -ATPase activities.


CONCLUSIONS
CSF concentrations of the sum of ASP metabolites corresponding to the intake of common, abuse or toxic doses (34 or 150 or 200mg/kg, respectively) of the additive significantly increased rat frontal cortex Na+, K+ -ATPase and pure enzyme activities. Cys or GSH completely or partially restored to normal both enzyme activities, possibly due to amelioration of the cellular GSH reduction from the action of MeOH, a metabolite of the sweetener and/or by their scavenging effect.
Simintzi
Irene
I
Department of Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece.
Schulpis
Kleopatra H
KH
Angelogianni
Panagoula
P
Liapi
Charis
C
Tsakiris
Stylianos
S
D000818:Animals; D000833:Animals, Suckling; D000975:Antioxidants / Q000494:pharmacology*; D001218:Aspartame / Q000493:pharmacokinetics / Q000494:pharmacology*; D001224:Aspartic Acid / Q000494:pharmacology; D001711:Biotransformation; D017301:Ca(2+) Mg(2+)-ATPase / Q000134:cerebrospinal fluid / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D010649:Phenylalanine / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013549:Sweetening Agents / Q000493:pharmacokinetics / Q000494:pharmacology*
D000975:Antioxidants; D013549:Sweetening Agents; D001224:Aspartic Acid; D010649:Phenylalanine; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D003545:Cysteine; D001218:Aspartame