title: The role of the glyoxalase pathway in reducing mesothelial toxicity of glucose degradation products.
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 degrees C, and then mixed with an equal volume of serum-free M199 medium and applied to HPMCin 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 inter-Leukin-6 generation. Exposure of HPMC to the GSH precursor L-2-oxothiazolidine-carboxylic acid increased cellular GSH and prevented the loss of GLO-I activity in response to H-PDF.
  
  
  CONCLUSIONS
  Exposure to conventional GDP-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 GDP-mediated toxicity.
authors.affiliation: Department of Pathophysiology, University Medical School, Poznań, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Korybalska
authors.forename: Justyna
authors.initials: J
authors.lastname: Wisniewska-Elnur
authors.forename: Joanna
authors.initials: J
authors.lastname: Trómińska
authors.forename: Achim
authors.initials: A
authors.lastname: Jörres
authors.forename: Andrzej
authors.initials: A
authors.lastname: Breborowicz
authors.forename: Janusz
authors.initials: J
authors.lastname: Witowski
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*
chemical_list: D007791:Lactoylglutathione Lyase; D005947:Glucose