L-2-oxothiazolidine-4-carboxylic acid modulates function of peritoneal mesothelial cells in vitro

The influence of the glutathione precursor, L-2-oxothiazolidine-4-carboxyli c acid (OTZ), on the function of human peritoneal mesothelial cells in vitr o, in conditions that mimic the in vivo effect of peritoneal dialysis solut ions on mesothelium, was studied. Mesothelial monolayers were exposed to di alysis fluids (Dianeal 1.36 or Dianeal 3.86; Baxter Healthcare Corp, Round Lake, IL) that were diluted gradually with pooled-effluent dialysate obtain ed from patients undergoing continuous ambulatory peritoneal dialysis, In v itro exposure of mesothelium to standard dialysis fluid enhances their susc eptibility to injury by hydrogen peroxide, OTZ added to dialysis solution i n concentrations of 1 mmol/L prevented the toxic effect of hydrogen peroxid e, probably by increasing intracellular glutathione, Mesothelial cells expo sed to dialysis fluid become activated, evidenced by increased release of i nterleukin-6 and hyaluronan, OTZ used in concentrations of 1 mmol/L reduced that effect. Furthermore, the addition of glucose to the culture medium in a concentration of 45 mmol/L inhibits the proliferation of mesothelial cel ls; the presence of OTZ, 1 mmol/L, partially prevents the inhibitory effect of glucose, The results presented in this report show that by augmenting t he intracellular concentration of glutathione in mesothelial cells by the a ddition of OTZ to the dialysis fluid, we can increase their resistance to t he acute toxicity of free radicals and long-term toxicity of glucose. In ad dition, mesothelial cells with an increased glutathione level are less acti vated after their exposure to dialysis fluid. (C) 1999 by the National Kidn ey Foundation, Inc.