Effect of glucose degradation products on human peritoneal mesothelial cell function.
Bioincompatibility of conventional glucose-based peritoneal dialysis fluids (PDF) has been partially attributed to the presence of glucose degradation products (GDP) generated during heat sterilization of PDF. Most previous studies on GDP toxicity were performed on animal and/or transformed cell lines, and the impact of GDP on peritoneal cells remains obscure. The short-term effects of six identified GDP on human peritoneal mesothelial cell (HPMC) functions were examined in comparison to murine L929 fibroblasts. Exposure of HPMC to acetaldehyde, formaldehyde, glyoxal, methylglyoxal, furaldehyde, but not to 5-hydroxymethyl-furfural, resulted in dose-dependent inhibition of cell growth, viability, and interleukin-1beta (IL-1beta)-stimulated IL-6 release; for several GDP, this suppression was significantly greater compared with L929 cells. Although the addition of GDP to culture medium at concentrations found in PDF had no major impact on HPMC function, the exposure of HPMC to filter-sterilized PDF led to a significantly smaller suppression of HPMC proliferation compared to that induced by heat-sterilized PDF. The growth inhibition mediated by filter-sterilized PDF could be increased after the addition of clinically relevant doses of GDP. These effects were equally evident in L929 cells. In conclusion, GDP reveal a significant cytotoxic potential toward HPMC that may be underestimated in test systems using L929 cells. GDP-related toxicity appears to be particularly evident in experimental systems using proliferating cells and the milieu of dialysis fluids. Thus, these observations may bear biologic relevance in vivo where HPMC are repeatedly exposed to GDP-containing PDF for extended periods of time.
Witowski
Janusz
J
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.|Department of Pathophysiology, University Medical School, Poznan, Poland.
Korybalska
Katarzyna
K
Department of Pathophysiology, University Medical School, Poznan, Poland.
Wisniewska
Justyna
J
Department of Pathophysiology, University Medical School, Poznan, Poland.
Breborowicz
Andrzej
A
Department of Pathophysiology, University Medical School, Poznan, Poland.
Gahl
Gerhard M
GM
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
Frei
Ulrich
U
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
Passlick-Deetjen
Jutta
J
Fresenius Medical Care, Bad Homburg, Germany.
Jörres
Achim
A
Department of Nephrology and Medical Intensive Care, Universitätsklinikum Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany.
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology; D005374:Filtration; D005947:Glucose / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D000093242:Interleukin-6 Inhibitors
D015314:Dialysis Solutions; D005947:Glucose; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors