Intracellular Glutathione in Human Peritoneal Mesothelial Cells Exposed in vitro to Dialysis Fluid

Abstract

Effect of peritoneal dialysis fluids on glutathione (GSH/GSSG) level in human peritoneal mesothelial cells was tested in in vitro experiments. To mimic in vivo conditions, cells were initially exposed to dialysis fluids (Dianeal 1.36%, Dianeal 2.27%, Dianeal 3.86%) that subsequently were diluted with dialysate effluent at time intervals. GSH/GSSG concentration in cells initially decreased but returned to normal values thereafter. This decrease in the intracellular concentration of glutathione was less when pH of the tested dialysis fluid was adjusted to 7.3. In further experiments with mesothelial cells exposed to Earle's salts solution supplemented with glucose and/or lactate, we have shown that in the presence of low pH, lactate is the main factor causing depletion of intracellular glutathione. When added to the dialysis solution at a concentration of 0.1 mM, L-2-oxothiazolidine-4-carboxylate, a precursor of glutathione, not only prevents the initial decrease in glutathione concentration but also augments the final intracellular level of this thiol.