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Neuronal damage and shortening of lifespan in C. elegans by peritoneal dialysis fluid: Protection by glyoxalase1

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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.
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Document Type: Research Article

Affiliations: 1: Fifth Medical Department, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany 2: Department of Medicine I and Clinical Chemistry, Heidelberg University, D-69120 Heidelberg, Germany 3: Department of Dermatology, Heidelberg University, D-69120 Heidelberg, Germany 4: Department of Nephrology, Centre Hospitalier du Nord, 9080 Ettelbruck, Luxembourg 5: Department of Nephrology, Heidelberg University, D-69120 Heidelberg, Germany 6: Klinik für Nieren, Hochdruck und Autoimmunerkrankungen, Klinikum Stuttgart, D-70174 Stuttgart, Germany

Publication date: June 1, 2018

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