Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R,S-alpha-lipoic acid on glutathione content of myelomonocytic cells

BACKGROUND & AIMS: Several diseases are characterised by decreased glutathione (GSH) levels due to an enhanced formation of oxygen radicals. To increase GSH levels, the additional supply of GSH precursors was suggested. In this study we evaluated the potency of a single and combined administration of the GSH modulating substances glutamine (GLN), N-acetylcysteine (NAC), and glycine (GLY) as well as R,S-alpha-lipoic acid (LA) to enhance intracellular GSH content in a well-defined model system. RESULTS: Exposure of myelomonocytic U937 cells for 24 h to GLN revealed a 1.5-fold enhancement of GSH levels with a concomitant decrease in the formation of reactive oxygen species and lipid peroxidation. Addition of NAC stimulated GSH formation only at subphysiological GLN levels. GLY enhanced GSH levels under GLN starvation, but caused a diminution of GSH content under optimal GLN supply. LA in combination with 2 mmol/l GLN evoked a 3.6-fold enhancement of GSH content compared to GLN starved cells. CONCLUSION: These results demonstrate that the GSH content of U937 cells is dependent on the supply of GLN, NAC, LA, and GLY. Combinations of the single substances can enhance but also decrease the intracellular GSH content, which is of clinical importance when supplying GSH-modulating substances to patients.