Induction of 1,2-Dicarbonyl Compounds,Intermediates in the Formation of Advanced Glycation End-Products,during Heat-Sterilization of Glucose-Based Peritoneal Dialysis Fluids
Restricted accessResearch articleFirst published online July, 1999
Induction of 1,2-Dicarbonyl Compounds,Intermediates in the Formation of Advanced Glycation End-Products,during Heat-Sterilization of Glucose-Based Peritoneal Dialysis Fluids
To study the presence of 1,2-dicarbonyl compounds in peritoneal dialysis (PD) fluids, their concentration in effluents with increasing dwell time, and their role in the formation of advanced glycation end-products (AGEs).
Measurements
Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (HPLC) after derivatization to dimethoxyquinoxaline derivatives. Kinetics of the in vitro formation of AGEs upon incubation of 1,2-dicarbonyl compounds or PD fluids with albumin, with or without aminoguanidine, were measured by AGE fluorescence (excitation/emission wavelengths of 350 nm/430 nm).
Patients
AGEs and dicarbonyl compounds were measured in effluents collected from standardized 4-hour dwells from 8 continuous cycling peritoneal dialysis patients.
Results
In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the major dicarbonyl compound formed during the process of heat sterilization. The process also formed glyoxal (GO) and methylglyoxal (MGO), with the amount of 3-DG being approximately 25 – 60 times higher than GO and MGO. When incubated with albumin, the identified 1,2-dicarbonyl compounds rapidly formed AGEs. The formation of AGEs was more pronounced in conventional heat-sterilized PD fluids compared with filter-sterilized PD fluids, and was completely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO, and 3-DG decreased with increasing dwell time, with a concomitant increase in AGE fluorescence.
Conclusions
The dicarbonyl compounds 3-DG, MGO, and GO are potent promoters of AGE formation. The presence of these and possibly other dicarbonyl compounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitro AGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete inhibition by aminoguanidine. Because 3-DG, MGO, and GO are rapidly cleared from PD fluids during dialysis, these compounds may contribute to the in vivo AGE formation in PD patients.
WieslanderA.P., NordinM.K., KjellstrandP. T., BobergU.C.Toxicity of peritoneal dialysis fluids on cultured fibroblasts, L-929.Kidney Int1991; 40: 77–9.
2.
BronswijkH., VerbrughH.A., BosH.J., HeeziusE.C., OeP.L., Van der MeulenJ.Cytotoxic effects of commercial continuous ambulatory peritoneal dialysis (CAPD) fluids and of bacterial exoproducts on human mesothelial cells in vitro.Perit Dial Int1989; 9: 197–202.
3.
WieslanderA P., KjellstrandP.T., RippeB.Heat sterilization of glucose-containing fluids for peritoneal dialysis: biological consequences of chemical alterations.Perit Dial Int1995; 15(Suppl 1): S52–60.
4.
WieslanderA.P., NordinM.K., MartinsonE., KjellstrandP. T., BobergU.C.Heat sterilized PD fluids impair growth and inflammatory responses of cultured cell lines and human leukocytes.Clin Nephrol1993; 39: 343–8.
5.
JonassonP., BaggeU., WieslanderA., BraideM.Heat-sterilized PD fluid blocks leukocyte adhesion and increases flow velocity in rat peritoneal venules.Perit Dial Int1996; 16(Suppl 1): S137–40.
6.
Nilsson–ThorellC.B., MuscaluN., AndrenA.H.G., KjellstrandP.T.T., WieslanderA. P.Heat sterilization of fluids for peritoneal dialysis gives rise to aldehydes.Perit Dial Int1993; 13: 208–13.
7.
WieslanderA., ForsbackG., SvenssonE., LindenT.Cytotoxicity, pH, and glucose degradation products in four different brands of PD fluid. In: KhannaR., ed. Advances in peritoneal dialysis.Toronto: Peritoneal Dialysis Publications, 1996; 12: 57–60.
8.
KjellstrandP., MartinsonE., WieslanderA., HolmquistB.Development of toxic degradation products during heat sterilization of glucose-containing fluids for peritoneal dialysis: influence of time and temperature.Perit Dial Int1995; 15: 26–32.
9.
LeggeM., LashG.E., BirdS.D., WalkerR.J.Formaldehyde in heat sterilized peritoneal dialysis solutions: scavenging system for its removal.Perit Dial Int1998; 18: 228–31.
10.
WieslanderA P.Cytotoxicity of peritoneal dialysis fluid — is it related to glucose breakdown products?Nephrol Dial Transplant1996; 11: 958–9.
11.
WieslanderA., LindenT.Glucose degradation and cytotoxicity in PD fluids.Perit Dial Int1996; 16(Suppl 1): S114–18.
12.
WieslanderA.P., AndrenA.H., Nilsson–ThorellC., MuscaluN., KjellstrandP.T., RippeB.Are aldehydes in heat-sterilized peritoneal dialysis fluids toxic in vitro?Perit Dial Int1995; 15: 348–52.
13.
TopleyN., AlobaidiH.M.M., DaviesM., ColesG.A., WilliamsJ.D., LloydD.The effect of dialysate on peritoneal phagocyte oxidative metabolism.Kidney Int1988; 34: 404–11.
14.
LindenT., ForsbäckG., DeppischR., HenleT., WieslanderA.3-Deoxyglucosone, a promoter of advanced glycation end products in fluids for peritoneal dialysis.Perit Dial Int1998; 18: 290–3.
15.
BrownleeM., CeramiA., VlassaraH.Advanced glycosylation end products in tissues and the biochemical basis of diabetic complications.N Engl J Med1988; 318: 1315–21.
16.
EdelsteinD., BrownleeM.Mechanistic studies of advanced glycation end product inhibition by aminoguanidine.Diabetes1992; 41: 26–9.
17.
LoT.W., SelwoodT., ThornalleyP.J.The reaction of methylglyoxal with aminoguanidine under physiological conditions and prevention of methylglyoxal binding to plasma proteins.Biochem Pharmacol1994; 48: 1865–70.
18.
LambE.J., CattellW.R., DawnayA.B.In vitro formation of advanced glycation end products in peritoneal dialysis fluid.Kidney Int1995; 47: 1768–74.
19.
DawnayA.B., MillarD.J.Glycation and advanced glycation end-product formation with icodextrin and dextrose.Perit Dial Int1997; 17: 52–8.
20.
DawnayA.B.Advanced glycation end products in peritoneal dialysis.Perit Dial Int1996; 16(Suppl 1): S50–3.
21.
LambE., CattellW.R., DawnayA.B.Glycated albumin in serum and dialysate of patients on continuous ambulatory peritoneal dialysis.Clin Sci1993; 84: 619–26.
22.
YamadaK., MiyaharaY., HamaguchiK., NakayamaM., NakanoH., NozakiO.Immunohistochemical study of human advanced glycosylation end-products (AGE) in chronic renal diseases.Clin Nephrol1994; 42: 354–61.
23.
MahioutA., EhlerdingG., BrunkhorstR.Advanced glycation end-products in the peritoneal fluid and in the peritoneal membrane of continuous ambulant peritoneal dialysis patients.Nephrol Dial Transplant1996; 11(Suppl 5): 2–6.
24.
McLellanA.C., ThornalleyP.J.Synthesis and chromatography of 1,2-diamino-4,5-dimethoxybenzene, 6,7-dimethoxy-2-methylquinoxaline and 6,7-dimethoxy-2,3-dimethylquinoxaline for use in a liquid chromatographic fluorimetric assay of methylglyoxal.Anal Chim Acta1992; 263: 137–42.
25.
McLellanA.C., PhillipsS.A., ThornalleyP.J.The assay of methylglyoxal in biological systems by derivatization with 1,2-diamino-4,5-dimethoxybenzene.Anal Biochem1992; 206: 17–23.
26.
KhademH.E., HortonD., MeshrekiM.H., NashedM.A.New route for the synthesis of 3-deoxyaldos-2-uloses.Carbohydr Res1971; 17: 183–92.
27.
WolffS P., DeanR T.Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes.Biochem J1987; 245: 243–50.
28.
Wells–KnechtJ.K.J., ZyzakD.V., LitchfieldJ.E., ThorpeS., BaynesJ. W.Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose.Biochemistry1995; 34: 3702–9.
29.
NiwaT., KatsuzakiT., MomoiT., MiyazakiT., OgawaH., SaitoA.Modification of β2m with advanced glycation end products as observed in dialysis-related amyloidosis by 3-DG accumulating in uremic serum.Kidney Int1996; 49: 861–7.
30.
KatoH., van ChuyenN., ShinodaT., SekiyaF., HayaseF.Metabolism of 3-deoxyglucosone, an intermediate compound in the Maillard reaction, administered orally or intravenously to rats.Biochem Biophys Acta1990; 1035: 71–6.
31.
SatoK., InazuA., YamaguchiS., NakayamaT., DeyashikiY., SawadaH.Monkey 3-deoxyglucosone reductase: tissue distribution and purification of three multiple forms of the kidney enzyme that are identical with dihydrodiol dehydrogenase, aldehyde reductase and aldose reductase.Arch Biochem Biophys1993; 307: 286–94.
32.
OkadoA., KawasakiY., HasuikeY., TakahashiM., TeshimaT., FujiiJ.Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines.Biochem Biophys Res Commun1996; 225: 219–24.
33.
KangY., EdwardsL.G., ThornalleyP.J.Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA, G1, growth arrest and induction of apoptosis.Leuk Res1996; 20: 397–405.
34.
CheW., AsahiM., TakahashiM., KanetoH., OkadoA., HigashiyamaS.Selective induction of heparin-binding epidermal growth factor-like growth factor by methylglyoxal and 3-deoxyglucosone in rat aortic smooth muscle cells. The involvement of reactive oxygen species formation and a possible implication for atherogenesis in diabetes.J Biol Chem1997; 272: 18453–9.
35.
WestwoodM.E., ThornalleyP.J.Induction of synthesis and secretion of interleukin 1 beta in the human monocytic THP-1 cells by human serum albumins modified with methylglyoxal and advanced glycation end-products.Immunol Lett1996; 50: 17–21.
36.
AbordoE.A., ThornalleyP.J.Synthesis and secretion of tumour necrosis factor-alpha by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts.Immunol Lett1997; 58: 139–47.
37.
AbordoE.A., WestwoodM.E., ThornalleyP.J.Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts.Immunol Lett1996; 53: 7–13.
38.
EspositoC., GerlachH., BrettJ., SternD., VlassaraH.Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulation properties.J Exp Med1989; 170: 1387–407.
39.
WautierJ.L., ZoukourianC., ChappeyO., WautierM.P., GuillausseauP.J., CaoR.Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats.J Clin Invest1996; 1: 238–43.
40.
WieslanderA.P., DeppischR., SvenssonE., ForsbackG., SpeidelR., RippeB.In vitro biocompatibility of a heat-sterilized, low-toxic, and less acidic fluid for peritoneal dialysis.Perit Dial Int1995; 15: 158–64.
