Pyruvate neutralizes peritoneal dialysate cytotoxicity: maintained integrity and proliferation of cultured human mesothelial cells.
Toxic effects of commercially available peritoneal dialysate (PD) fluid include damage to mesothelial cells (MC), causing a severely disturbed proliferation of cultured MC. We investigated the injury to the cell membrane (by release of lactate dehydrogenase, LDH), the proliferation (by cell counts and by 3H-thymidine incorporation), and optional the cytokine generation (by IL-1 receptor-antagonist production, IL-1 ra) of cultured human MC during the 48 hours after a 30 minute exposure to PD containing either 35 mmol/liter sodium lactate or sodium pyruvate. All solutions had a pH of 5.2 to 5.6 and were composed as standard PD. Glucose contents of 1.36 and 3.86 mmol/liter were tested. After exposure to the lactate-PD containing 1.36% glucose, LDH activity was increased by more than 30%, proliferation of MC was inhibited by more than 30%, and IL-1 ra production was reduced significantly when compared to pyruvate-PD and the control solution. After preincubation with 3.86% glucose containing PD, all negative effects became even more pronounced in the lactate group whereas the MC maintained their integrity, rate of proliferation and IL-1 ra release after pre-exposure to pyruvate containing PD. These results suggest that the acute toxic effects of commercially available PD on the integrity, proliferation and IL-1 ra production of MC can be avoided by the use of sodium pyruvate instead of sodium lactate.
Brunkhorst
R
R
Division of Nephrology, Hannover Medical School, Germany.
Mahiout
A
A
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000009:adverse effects*; D004848:Epithelium / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000009:adverse effects; D019344:Lactic Acid; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects*; D011773:Pyruvates / Q000494:pharmacology*; D019289:Pyruvic Acid; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D013936:Thymidine / Q000378:metabolism
D015314:Dialysis Solutions; D007773:Lactates; D011773:Pyruvates; D017472:Receptors, Interleukin-1; D019344:Lactic Acid; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D013936:Thymidine