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3,4-Dideoxyglucosone-3-ene (3,4-DGE): A cytotoxic glucose degradation product in fluids for peritoneal dialysis

Linden, T; Cohen, Arieh LU ; Deppisch, R; Kjellstrand, P and Wieslander, A (2002) In Kidney International 62(2). p.697-703
Abstract
Background. Bioincompatible glucose degradation products (GDPs) in fluids for peritoneal dialysis (PD) develop during sterilization and storage. Their biological activity has successfully been monitored through the use of various in vitro methods but their molecular and chemical nature is less well understood. Many GDPs are highly reactive carbonyl compounds. Although some of the identified GDPs are extremely cytotoxic, none of them actually possess cytotoxicity at the concentrations found in PD fluids. Thus, the GDP responsible for the toxicity in PD fluids has not yet been identified. The intention of the present work was to investigate to what extent the unsaturated dicarbonyl compound, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was present... (More)
Background. Bioincompatible glucose degradation products (GDPs) in fluids for peritoneal dialysis (PD) develop during sterilization and storage. Their biological activity has successfully been monitored through the use of various in vitro methods but their molecular and chemical nature is less well understood. Many GDPs are highly reactive carbonyl compounds. Although some of the identified GDPs are extremely cytotoxic, none of them actually possess cytotoxicity at the concentrations found in PD fluids. Thus, the GDP responsible for the toxicity in PD fluids has not yet been identified. The intention of the present work was to investigate to what extent the unsaturated dicarbonyl compound, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was present in PD fluids, and if it could be responsible for the in vitro effects on L-929 fibroblast cells. Methods. A commercial preparation of 3,4-DGE and two different liquid chromatography methods were used for the chemical identification and quantification. In vitro bioincompatibility was determined as inhibition of cell growth using the L-929 fibroblast cell line. Results. 3,4-DGE was present in conventionally manufactured PD fluids at a concentration of 9 to 22 mumol/L. In the newly developed PD fluid, Gambrosol trio, the concentrations were 0.3 to 0.7 mumol/L. When added as synthetic 3,4-DGE to cell growth media at the concentrations measured in conventional PD fluids, the inhibition of cell growth was significantly lower than for that seen with the conventional fluids. However, in the conventional PD fluids the total amount of 3,4-DGE available for toxic reactions most probably was higher than that measured, because 3,4-DGE was freshly recruited from a molecular pool when consumed. The speed of this recruitment was high enough to explain most of the growth inhibition seen for heat-sterilized PD fluids. Conclusion. 3,4-DGE is present in conventional PD fluids at a concentration between 9 and 22 mumol/L, and is the most biologically active of all GDPs identified to date. Thus, it is the main candidate to be held responsible for the clinical bioincompatibility caused by conventionally manufactured PD fluids. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
toxicity, glucose, 3, dialysate, biocompatibility, peritoneal dialysis, 4-DGE
in
Kidney International
volume
62
issue
2
pages
697 - 703
publisher
Nature Publishing Group
external identifiers
  • wos:000176746600039
  • pmid:12110035
  • scopus:0035991599
ISSN
1523-1755
DOI
10.1046/j.1523-1755.2002.00490.x
language
English
LU publication?
yes
id
63da40b1-c655-409e-a32b-cc69ce870095 (old id 333663)
date added to LUP
2007-10-31 11:03:49
date last changed
2017-11-05 04:25:42
@article{63da40b1-c655-409e-a32b-cc69ce870095,
  abstract     = {Background. Bioincompatible glucose degradation products (GDPs) in fluids for peritoneal dialysis (PD) develop during sterilization and storage. Their biological activity has successfully been monitored through the use of various in vitro methods but their molecular and chemical nature is less well understood. Many GDPs are highly reactive carbonyl compounds. Although some of the identified GDPs are extremely cytotoxic, none of them actually possess cytotoxicity at the concentrations found in PD fluids. Thus, the GDP responsible for the toxicity in PD fluids has not yet been identified. The intention of the present work was to investigate to what extent the unsaturated dicarbonyl compound, 3,4-dideoxyglucosone-3-ene (3,4-DGE) was present in PD fluids, and if it could be responsible for the in vitro effects on L-929 fibroblast cells. Methods. A commercial preparation of 3,4-DGE and two different liquid chromatography methods were used for the chemical identification and quantification. In vitro bioincompatibility was determined as inhibition of cell growth using the L-929 fibroblast cell line. Results. 3,4-DGE was present in conventionally manufactured PD fluids at a concentration of 9 to 22 mumol/L. In the newly developed PD fluid, Gambrosol trio, the concentrations were 0.3 to 0.7 mumol/L. When added as synthetic 3,4-DGE to cell growth media at the concentrations measured in conventional PD fluids, the inhibition of cell growth was significantly lower than for that seen with the conventional fluids. However, in the conventional PD fluids the total amount of 3,4-DGE available for toxic reactions most probably was higher than that measured, because 3,4-DGE was freshly recruited from a molecular pool when consumed. The speed of this recruitment was high enough to explain most of the growth inhibition seen for heat-sterilized PD fluids. Conclusion. 3,4-DGE is present in conventional PD fluids at a concentration between 9 and 22 mumol/L, and is the most biologically active of all GDPs identified to date. Thus, it is the main candidate to be held responsible for the clinical bioincompatibility caused by conventionally manufactured PD fluids.},
  author       = {Linden, T and Cohen, Arieh and Deppisch, R and Kjellstrand, P and Wieslander, A},
  issn         = {1523-1755},
  keyword      = {toxicity,glucose,3,dialysate,biocompatibility,peritoneal dialysis,4-DGE},
  language     = {eng},
  number       = {2},
  pages        = {697--703},
  publisher    = {Nature Publishing Group},
  series       = {Kidney International},
  title        = {3,4-Dideoxyglucosone-3-ene (3,4-DGE): A cytotoxic glucose degradation product in fluids for peritoneal dialysis},
  url          = {http://dx.doi.org/10.1046/j.1523-1755.2002.00490.x},
  volume       = {62},
  year         = {2002},
}