Neuronal damage and shortening of lifespan in C.�elegans by peritoneal dialysis fluid: Protection by glyoxalase‑1

Glucose and glucose degradation products (GDPs), contained in peritoneal dialysis (PD) fluids, contribute to the formation of advanced glycation end-products (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 glyoxalase-1 (GLO1) has beneficial effects on GDP-mediated toxicity. The aim of the current study was to analyze systemic detrimental effects of PD fluids and their prevention by glyoxlase-1. Wild-type and GLO1-overexpressing Caenorhabditis elegans ( C. elegans ) were cultivated in the presence of low- and high-GDP 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 high-GDP fluids caused reduction of neuronal integrity by 34 (P<0.05) and 41% (P<0.05). Cultivation of animals in the presence of low-GDP 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 glucose-induced lifespan reduction, neurostructural damage and neurofunctional damage under low-GDP-conditions. 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 low-GDP environment. These data emphasize the relevance of the GLO1 detoxifying pathway as a potential therapeutic target in the treatment of reactive metabolite-mediated pathologies.