TY - JOUR
T1 - The role of the glyoxalase pathway in reducing mesothelial toxicity of glucose degradation products
AU - Korybalska, Katarzyna
AU - Wisniewska-Elnur, Justyna
AU - Trómińska, Joanna
AU - Jörres, Achim
AU - Brȩborowicz, Andrzej
AU - Witowski, Janusz
PY - 2006
Y1 - 2006
N2 - ◆ 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.
AB - ◆ 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.
KW - Biocompatibility
KW - Dialysis fluids
KW - Glucose degradation products
KW - Glutathione
KW - Glyoxalase
KW - Mesothelial cells
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U2 - 10.1177/089686080602600223
DO - 10.1177/089686080602600223
M3 - Article
C2 - 16623434
AN - SCOPUS:33747120699
SN - 0896-8608
VL - 26
SP - 259
EP - 265
JO - Peritoneal Dialysis International
JF - Peritoneal Dialysis International
IS - 2
ER -