L-Cysteine and glutathione restore the reduction of rat hippocampal Na+, K+-ATPase activity induced by aspartame metabolites PY2007 IR94 教材

L-Cysteine and glutathione restore the reduction of rat hippocampal Na+, K+-ATPase activity induced by aspartame metabolites PY2007 IR94 教材

Irene Simintzi et al. Toxicology. 2007.

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Toxicology

. 2007 Jul 31;237(1-3):177-183.

doi: 10.1016/j.tox.2007.05.011. Epub 2007 May 18.

Authors

Irene Simintzi 1, Kleopatra H Schulpis 2, Panagoula Angelogianni 1, Charis Liapi 3, Stylianos Tsakiris 4

Affiliations

1Department of Experimental Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece.

2Institute of Child Health, Research Center, "Aghia Sophia" Children's Hospital, 11527 Athens, Greece.

3Department of Experimental Pharmacology, Medical School, Athens University, Athens, Greece.

4Department of Experimental Physiology, Medical School, Athens University, P.O. Box 65257, GR-15401 Athens, Greece. Electronic address: stsakir@cc.uoa.gr.

PMID: 17602817

DOI: 10.1016/j.tox.2007.05.011

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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.