title: L-Cysteine and glutathione restore the reduction of rat hippocampal Na+, K+-ATPase activity induced by aspartame metabolites.
abstract: Studies have implicated aspartame (ASP) ingestion in neurological problems. The aim of this study was to evaluate hippocampal Na(+),K(+)-ATPase and Mg(2+)-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 Mg(2+)-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 200mg/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 Mg(2+)-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.
authors.affiliation: Department of Experimental Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Simintzi
authors.affiliation: Institute of Child Health, Research Center, "Aghia Sophia" Children's Hospital, 11527 Athens, Greece.
authors.forename: Kleopatra H
authors.initials: KH
authors.lastname: Schulpis
authors.affiliation: Department of Experimental Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece.
authors.forename: Panagoula
authors.initials: P
authors.lastname: Angelogianni
authors.affiliation: Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece.
authors.forename: Charis
authors.initials: C
authors.lastname: Liapi
authors.affiliation: Department of Experimental Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece. Electronic address: stsakir@cc.uoa.gr.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
mesh_terms: D000818:Animals; D000833:Animals, Suckling; D001218:Aspartame / Q000009:adverse effects / Q000378:metabolism; D001224:Aspartic Acid / Q000009:adverse effects / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005978:Glutathione / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D066298:In Vitro Techniques; D008297:Male; D000432:Methanol / Q000009:adverse effects / Q000378:metabolism; D010649:Phenylalanine / Q000009:adverse effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013549:Sweetening Agents / Q000009:adverse effects / Q000378:metabolism
chemical_list: D013549:Sweetening Agents; D001224:Aspartic Acid; D010649:Phenylalanine; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D003545:Cysteine; D000432:Methanol; D001218:Aspartame