l-Cysteine and glutathione restore the reduction of rat hippocampal Na+, K+-ATPase activity induced by aspartame metabolites

Studies have implicated aspartame (ASP) ingestion in neurological problems. The aim of this study was to evaluate hippocampal Na+,K+-ATPase and Mg2+-ATPase activities after incubation with ASP or each of ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately.Suckling rat hippocampal homogenates or pure Na+,K+-ATPase were incubated with ASP metabolites. Na+,K+-ATPase and Mg2+-ATPase activities were measured spectrophotometrically. Incubation of hippocampal or pure Na+,K+-ATPase with ASP concentrations (expected in the cerebrospinal fluid (CSF)) after ASP consumption of 34, 150 or 200 mg/kg resulted in hippocampal enzyme activity reduction of 26%, 50% or 59%, respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation with hippocampal homogenate of each one of the corresponding in the CSF ASP metabolites related to the intake of common, high/abuse doses of the sweetener, inhibited Na+,K+-ATPase, while pure enzyme was activated. Hippocampal Mg2+-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) in ASP mixtures, related with high/toxic doses of the sweetener, completely or partially restored the inactivated membrane Na+,K+-ATPase, whereas the activated pure enzyme activity returned to normal.CSF concentrations of ASP metabolites related to common, abuse/toxic doses of the additive significantly reduced rat hippocampal Na+,K+-ATPase activity, whereas pure enzyme was activated. Cys or GSH completely or partially restored both enzyme activities.