Red blood cells as a physiological source of glutathione for extracellular fluids

Plasma low molecular mass thiols are represented by glutathione, cysteine, cysteinylglycine and homocysteine. The physiological mechanisms responsible for maintaining the homeostasis of these compounds in the intracellular and extracellular spaces have not been fully clarified. Erythrocytes possess the enzymatic machinery to synthesize glutathione and an efflux of glutathione disulfide and glutathione conjugates from erythrocytes under various conditions occurs. In this study, the property of red blood cells (RBCs) to export low molecular mass thiols has been assessed. Plasma concentration of low molecular mass thiols has been measured in healthy volunteers by HPLC and a significant correlation with RBC number has been observed for glutathione and cysteinylglycine. A sustained export of reduced glutathione has been observed (about 21 nmol/h/ml RBCs) together with a lower, though significant, efflux of both cysteine and homocysteine. These results suggest that erythrocytes can contribute significantly to the extracellular pool of glutathione (GSH), thus cooperating with liver and other tissues to the dynamics of inter-organ GSH metabolism.