Evaluation of Glyoxal and Methylglyoxal Levels in Uremic Patients under Peritoneal Dialysis

Abstract

Advanced glycation end products (AGEs) accumulate in serum and tissues of patients with chronic renal failure, even in the absence of diabetes, and a different clearance of these species has been observed by hemodialysis and peritoneal dialysis (CAPD). Furthermore, it has been shown that not only AGE but also 1,2-dicarbonyl compounds are formed during heat sterilization of glucose-based peritoneal dialysis fluids. Therefore, we investigated the level of some AGEs (pentosidine and free pentosidine) and dicarbonyl compounds (glyoxal and methylglyoxal) in end-stage renal disease patients subjected to peritoneal dialysis. Samples (20 from healthy subjects, 16 from uremic patients before and after 12 h of peritoneal dialysis) were analyzed, and the plasma and dialysate levels of glyoxal, methylglyoxal, pentosidine, and free pentosidine were determined. In plasma of uremic patients, mean values of pentosidine showed a small decrease after dialysis and were always higher than those of healthy control subjects. An analogous trend was observed for free pentosidine. In the case of peritoneal dialysate, no pentosidine and free pentosidine were found at time zero, whereas both compounds were detected after 12 h of dialysis. Glyoxal and methylglyoxal mean levels showed a decrease in plasma after dialysis even if their values were always higher than those of healthy control subjects. Surprisingly, an analogous trend was observed also in dialysate. These results might indicate that glyoxal and methylglyoxal already present in the dialysis fluid react with the peritoneal matrix proteins, accounting for the gradual loss of peritoneal membrane function that is often observed in patients subjected to CAPD for a long time.

Carbonylation Induces Heterogeneity in Cardiac Ryanodine Receptor Function in Diabetes Mellitus

“…At low micromolar concentrations, RCS regulate cell proliferation, prevent aggregation of proteins, and tag proteins for degradation (Nagaraj et al, 2003;Barrera et al, 2004;Dalle-Donne et al, 2006;Wong et al, 2010;Segré and Chiocca, 2011). In diabetes, production of RCS, including lipid-derived malondialdehyde and 4-hydroxynonenal and glucose-derived glyoxal, deoxyglucosone, and methylglyoxal (MGO), increases (Slatter et al, 2004;Lapolla et al, 2005;Fosmark et al, 2009;Vicentini et al, 2011). These electrophiles react with susceptible basic amino acids on proteins to form RCS adducts.…”

Endothelial Na + /H + exchanger NHE1 participates in redox-sensitive leukocyte recruitment triggered by methylglyoxal

“…Excessive levels of the glycolysis metabolite methylglyoxal (MG) in vivo, that contribute to increased carbonyl stress, are associated with conditions such as diabetes, renal failure, obesity and metabolic syndrome [4][5][6][7][8][9]. In diabetes, increased levels of MG are implicated in the pathogenesis of vascular complications such as hypertension [10], impaired microcirculation [11], and thrombosis [12].…”

Reactive carbonyl compounds (RCCs) cause aggregation and dysfunction of fibrinogen

“…Physiological concentrations of methylglyoxal (0.1 µmol/L, Lapolla et al, 2005), glyoxal (0.2 µmol/L, Lapolla et al, 2005) and malondialdehyde (600.0 µmol/L, Nielsen et al, 1997;Lapolla et al, 2005;Igarashi et al, 2006;Andrades et al, 2009) are too low to have a significant effect on fibrinogenesis, unless their blood concentrations were higher than 1 mmol/L. Of note, the concentration of glycolaldehyde is the highest of these RCCs.…”

“…At the physiological concentrations the RCCs in blood (Nielsen et al, 1997;Lapolla et al, 2005;Igarashi et al, 2006;Andrades et al, 2009), only glycolaldehyde shows a significant effect on disturbing fibrinogen-© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012 nesis. However, under the same conditions, glycolaldehyde and acrolein disrupted fibrinogenesis and suppress human blood (plasma) coagulation more strongly than other RCCs.…”

“…These RCCs all have an active aldehyde group which readily reacts with the side chains of lysinyl and argininyl residues in proteins. These RCCs are present in the blood and their concentrations under physiological conditions have been determined; the order from the highest concentration to the lowest concentration in human plasma is glycolaldehyde (Andrades et al, 2009), malondialdehyde (Nielsen et al, 1997), acrolein (Igarashi et al, 2006), glyoxal and methylglyoxal (Lapolla et al, 2005). Investigations of the effects of RCCs on the conformation and function of fibrinogen are necessary to clarify the mechanisms of hematologic diseases related to RCCs.…”