Pyruvate neutralizes peritoneal dialysate cytotoxicity: Maintained integrity and proliferation of cultured human mesothelial cells

Abstract

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.

Protective Effect of Pyruvate upon Cultured Mesothelial Cells Exposed to 2 m<i>M</i> Hydrogen Peroxide

“…So far, the evidence presented in this study, in addition to that previously reported by Brunkhorst and Mahiout [14, 15], is one more piece of information pointing at pyruvate as a possible protective buffer for peritoneal dialysis solutions. This approach finds further support from evidence indicating that pyruvate is freely diffusible from the intravascular to the intercellular, intracellular and mitochondrial compartments [40, 48, 49].…”

“…Studies done in human mesothelial cells in culture [13]detected the presence of intracellular antioxidant capability. Other in vitro studies [14, 15, 16]showed that pyruvate anions can neutralize the cytotoxic effects of peritoneal dialysis fluids upon cultured mesothelial cells that showed, unlike observations made using lactated solutions, increased proliferation and IL-6 production. We speculated that this additional information could be, at least in part, explained on the basis of the scavenger effect of pyruvate upon oxidants.…”

Effects of New Peritoneal Dialysis Solutions on Leukocyte Recruitment in the Rat Peritoneal Membrane

“…As NAD + is an essential electron acceptor in glycolysis, its exhaustion may paralyze the glycolysis pathway [24, 25]. Furthermore, there is evidence that lactate can modulate cell function by accelerating the glucose-driven polyol pathway and intracellular sorbitol accumulation [26, 27]. Lactate – alone or in conjunction with glucose – augmented HPMC activation, which could be blocked by the aldose reductase inhibitor sorbinil, thus indicating the involvement of the polyol pathway [28].…”

Comparative in vitro Study of Different Peritoneal Dialysis Solutions on Cytokine Production by Peripheral Blood Mononuclear Cells

“…Between the hypertonic glucose-based solutions, we found a significantly higher release of the cytokines constitutively released by PBMCs incubated in pyruvate-buffered solutions (p = 0.01), but no difference when the cells were stimulated with LPS. In an in vitro model of cultured human mesothelial cells, pyruvate neutralizes PD cytotoxicity and this effect is even more pronounced with the hypertonic glucose solution [37]. …”