Glucose and glucose degradation products (GDPs), contained in peritoneal dialysis (PD) fluids, contribute to the formation of advanced glycation endproducts (AGEs). Local damaging effects, resulting in functional impairment of the peritoneal membrane, are well studied. It is also supposed
that detoxification of AGE precursors by glyoxalase1 (GLO1) has beneficial effects on GDPmediated toxicity. The aim of the current study was to analyze systemic detrimental effects of PD fluids and their prevention by glyoxlase1. Wildtype and GLO1overexpressing Caenorhabditis elegans (C. elegans)
were cultivated in the presence of low and highGDP PD fluids containing 1.5 or 4% glucose. Lifespan, neuronal integrity and neuronal functions were subsequently studied. The higher concentrations of glucose and GDP content resulted in a decrease of maximum lifespan by 2 (P<0.01)
and 9 days (P<0.001), respectively. Exposure to low and highGDP fluids caused reduction of neuronal integrity by 34 (P<0.05) and 41% (P<0.05). Cultivation of animals in the presence of lowGDP fluid containing 4% glucose caused significant impairment of neuronal function,
reducing relative and absolute head motility by 58.5 (P<0.01) and 56.7% (P<0.01), respectively; and relative and absolute tail motility by 55.1 (P<0.05) and 55.0% (P<0.05), respectively. Taken together, GLO1 overexpression protected from glucoseinduced lifespan reduction, neurostructural
damage and neurofunctional damage under lowGDPconditions. In conclusion, both glucose and GDP content in PD fluids have systemic impact on the lifespan and neuronal integrity of C. elegans. Detoxification of reactive metabolites by GLO1 overexpression was sufficient to protect lifespan,
neuronal integrity and neuronal function in a lowGDP environment. These data emphasize the relevance of the GLO1 detoxifying pathway as a potential therapeutic target in the treatment of reactive metabolitemediated pathologies.
No Reference information available - sign in for access.
No Citation information available - sign in for access.
No Supplementary Data.
No Article Media
Document Type: Research Article
Fifth Medical Department, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany
Department of Medicine I and Clinical Chemistry, Heidelberg University, D-69120 Heidelberg, Germany
Department of Dermatology, Heidelberg University, D-69120 Heidelberg, Germany
Department of Nephrology, Centre Hospitalier du Nord, 9080 Ettelbruck, Luxembourg
Department of Nephrology, Heidelberg University, D-69120 Heidelberg, Germany
Klinik für Nieren, Hochdruck und Autoimmunerkrankungen, Klinikum Stuttgart, D-70174 Stuttgart, Germany
Publication date: June 1, 2018
More about this publication?
Biomedical Reports is a new, bimonthly, peer-reviewed journal, dedicated to publishing research across all fields of biology and medicine, including pharmacology, pathology, gene therapy, genetics, microbiology, neurosciences, infectious diseases, molecular cardiology and molecular surgery. The journal provides a home for original research, case reports and review articles.
- Editorial Board
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Information for Advertisers
- Terms & Conditions
- Ingenta Connect is not responsible for the content or availability of external websites