The role of the glyoxalase pathway in reducing mesothelial toxicity of glucose degradation products

Katarzyna Korybalska, Justyna Wisniewska-Elnur, Joanna Trómińska, Achim Jörres, Andrzej Brȩborowicz, Janusz Witowski

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6 Scopus citations

Abstract

◆ Background: The glucose degradation products (GDP) presentin conventional peritoneal dialysis fluids (PDF) may exert adverse effects toward human peritoneal mesothelial cells (HPMC). Some GDP can be detoxified by the glyoxalase/glutathione pathway. It has been shown that the addition of glyoxalase I (GLO-I) and reduced glutathione (GSH) to PDF effectively eliminates GDP. We have therefore examined the GLO-I/GSH system in HPMC and assessed the impact of GLO-I/GSH-treated PDF on the viability and function of HPMC. ◆ Methods: Heat-sterilized PDF (H-PDF) was incubated in the presence or absence of GLO-I and GSH for 1 hour at 37°C, and then mixed with an equal volume of serum-free M199 medium and applied to HPMC in culture. After 24 hours, HPMC were assessed for viability, the release of interleukin-6, GLO-I activity, and cellular glutathione. The effects were compared to those exerted by filter-sterilized PDF (F-PDF),which was devoid of GDP. ◆ Results: Exposure of HPMC to H-PDF resulted in reduced GlO-I activity, GSH depletion, and a decrease in cell viability. Pretreatment of H-PDF with either a combination of GLO-I and GSH or GSH alone markedly reduced inhibitory effects of H-PDF toward HPMC, as measured by cell viability and interleukin-6 generation. Exposure of HPMC to the GSH precursor L-2-oxothiazolidine-carboxytic acid increased cellular GSH and prevented the loss of GLO-I activityin response to H-PDF. ◆ Conclusions: Exposure to conventional GOP-rich PDF impairs the activity of the glyoxalase/glutathione system in HPMC. Pretreatment of PDF with GSH or replenishment of cellular GSH protects HPMC against GOP-mediated toxicity.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalPeritoneal Dialysis International
Volume26
Issue number2
Publication statusPublished - Mar 1 2006

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Keywords

  • Biocompatibility
  • Dialysis fluids
  • Glucose degradation products
  • Glutathione
  • Glyoxalase
  • Mesothelial cells

ASJC Scopus subject areas

  • Nephrology

Cite this

Korybalska, K., Wisniewska-Elnur, J., Trómińska, J., Jörres, A., Brȩborowicz, A., & Witowski, J. (2006). The role of the glyoxalase pathway in reducing mesothelial toxicity of glucose degradation products. Peritoneal Dialysis International, 26(2), 259-265.