Structure- and concentration-specific assessment of the physiological reactivity of alpha-dicarbonyl glucose degradation products in peritoneal dialysis fluids

Journal article


Publication Details

Author(s): Distler L, Georgieva A, Kenkell I, Huppert J, Pischetsrieder M
Journal: Chemical Research in Toxicology
Publisher: American Chemical Society
Publication year: 2014
Volume: 27
Pages range: 1421-1430
ISSN: 0893-228X


Abstract


In peritoneal dialysis (PD), glucose degradation products (GDPs), which are formed during heat sterilization of dialysis fluids, lead to structural and functional changes in the peritoneal membrane, which eventually result in the loss of its ultrafiltration capacity. To determine the molecular mechanisms behind these processes, the present study tested the influence of the six major α-dicarbonyl GDPs in PD fluids, namely, glyoxal, methylglyoxal, 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 3,4-dideoxyglucosone-3-ene (3,4-DGE), and glucosone with respect to their potential to impair the enzymatic activity of RNase A as well as their effects on cell viability. For comprehensive risk assessment, the α-dicarbonyl GDPs were applied separately and in concentrations as present in conventional PD fluids. Thus, it was shown that after 5 days, glucosone impaired RNase A activity most distinctly (58% remaining activity, p < 0.001 compared to that of the control), followed by 3,4-DGE (62%, p < 0.001), 3-DGal (66%, p < 0.001), and 3-DG (76%, p < 0.01). Methylglyoxal and glyoxal caused weaker inactivation with significant effects only after 10 days of incubation (79%, 81%, p < 0.001). Profiling of the advanced glycation end products formed during the incubation of RNase A with methylglyoxal revealed predominant formation of the arginine modifications imidazolinone, CEA/dihydroxyimidazoline, and tetrahydropyrimidine at Arg10, Arg33, Arg39, and Arg85. Particularly, modification at Arg39 may severely affect the active site of the enzyme. Additionally, structure- and concentration-specific assessment of the cytotoxicity of the α-dicarbonyl GDPs was performed. Although present at very low concentration, the cytotoxic effect of PD fluids after 2 days of incubation was exclusively caused by 3,4-DGE (14% cell viability, p < 0.001). After 4 days of incubation, 3-DGal (13% cell viability, p < 0.001), 3-DG (24%, p < 0.001), and, to a lower extent, glyoxal and methylglyoxal (both 57%, p < 0.01) also reduced cell viability significantly. In conclusion, 3,4-DGE, 3-DGal, and glucosone appear to be the most relevant parameters for the biocompatibility of PD fluids. © 2014 American Chemical Society.



FAU Authors / FAU Editors

Distler, Leonie Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)
Pischetsrieder, Monika Prof. Dr.
Lehrstuhl für Lebensmittelchemie (Henriette-Schmidt-Burkhardt Lehrstuhl)


Additional Organisation
Emil-Fischer-Zentrum (Emil Fischer Center)


How to cite

APA:
Distler, L., Georgieva, A., Kenkell, I., Huppert, J., & Pischetsrieder, M. (2014). Structure- and concentration-specific assessment of the physiological reactivity of alpha-dicarbonyl glucose degradation products in peritoneal dialysis fluids. Chemical Research in Toxicology, 27, 1421-1430. https://dx.doi.org/10.1021/tx500153n

MLA:
Distler, Leonie, et al. "Structure- and concentration-specific assessment of the physiological reactivity of alpha-dicarbonyl glucose degradation products in peritoneal dialysis fluids." Chemical Research in Toxicology 27 (2014): 1421-1430.

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Last updated on 2018-11-07 at 20:23