The Protective Effect of L-Cysteine and Glutathione on the Adult and Aged Rat Brain (Na super(+),K super(+))-ATPase and Mg super(2+)-ATPase Activities in Galactosemia In Vitro

• Published in: Metabolic brain disease Vol. 20; no. 1; pp. 87 - 95
• Main Authors: Tsakiris, Stylianos, Carageorgiou, Haris, Schulpis, Kleopatra H
• Format: Journal Article
• Language: English
• Published: 01-03-2005
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-005-2480-3

The aim of this study was to evaluate whether the addition of the antioxidants L-cysteine (Cys) or the reduced glutathione (GSH) could reverse the alterations of brain total antioxidant status (TAS) and the modulated activities of the enzymes (Na super(+),K super(+))-ATPase, and Mg super(2+)-ATPase in adult or aged rat brain homogenates induced by galactosemia in vitro. Mixture A [mix. A: galactose-1-phosphate (Gal-1-P, 2 mM) plus galactitol (Galtol, 2 mM) plus galactose (Gal, 4 mM) = classical galactosemia] or mixture B [mix. B: Galtol (2 mM) plus Gal (1 mM) = galactokinase deficiency galactosemia] were preincubated in the presence or absence of Cys (0.83 mM) or GSH (0.83 mM) with adult or aged brain homogenates at 37 super([compfn])C for 1 h. TAS and the enzyme activities were determined spectrophotometrically. Mix. A or mix. B preincubation with the adult brain resulted in a significant (Na super(+),K super(+))-ATPase inhibition (-30%) and a Mg super(2+)-ATPase stimulation (+300% and +33%, respectively), whereas lower modifications of the enzyme activities (p < 0.001) were found in the aged brain. Gal mixtures decreased TAS by 40% (p < 0.001) and by 20% (p < 0.01) in adult and aged samples, respectively. The antioxidants significantly increased TAS resulting in the reversion of (Na super(+),K super(+))-ATPase inhibition and Mg super(2+)-ATPase stimulation by mix. B only. The inhibitory effect of Gal and its derivatives on brain (Na super(+),K super(+))-ATPase and their stimulatory effect on Mg super(2+)-ATPase are being decreased with age, probably due to the producion of free radicals. Cys and GSH increased TAS resulting in a reversion of the inhibited (Na super(+),K super(+))-ATPase in both models of the in vitro galactosemia and the stimulated Mg super(2+)-ATPase in galactokinase deficiency galactosemia only.