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Background/Aim:Toxicity with advanced glycation end products (AGEs) is a major problem in uremic patients. Treatment with peritoneal dialysis (PD) exacerbates AGE formation as a result of bioincompatibility of the conventional peritoneal dialysis fluid (PDF). The presence of glucose degradation products (GDPs) in PDF is the main cause of its bioincompatibility. Carnosine is an endogenous dipeptide with a powerful antiglycation/antioxidant activity. In an attempt to improve PDF biocompatibility, we evaluated the effect of carnosine in human peritoneal mesothelial cells (HPMC) incubated with PDF or GDPs in vitro. Methods: HPMC were incubated for short or prolonged time with PDF in the presence or absence of carnosine. Similarly, HPMC were incubated in the same condition but with a combination of GDPs. Following the incubation, cells were tested for their viability, protein carbonyl content and reactive oxygen species (ROS) production. Results: Results demonstrated a significant protective effect of carnosine to HPMC in both acute and chronic conditions with PDF or GDPs as judged by the enhancement of cell viability, preserved protein from modification and decreased ROS production. Conclusion: Carnosine enhanced HPMC viability against the toxic effect of GDPs probably through protection of cellular protein from modification and from ROS-mediated oxidative damage. The salutary effect of carnosine may render it a desirable candidate for improving PDF biocompatibility and reducing AGE complications in PD patients.

Background Formation of advanced glycation end-products (AGEs) is a major problem in uremic patients treated with peritoneal dialysis (PD). Application of additives with known anti-glycosylation properties to PD fluid may be beneficial in minimizing the formation of AGEs. This study aimed to evaluate the effect of carnosine and its related peptides homocarnosine and anserine against the formation of AGEs in PD fluid. Methods PD solutions (1.5% dextrose) were incubated with human serum albumin (HSA) or collagen (type IV) with or without 10 mmol/L of each of carnosine, anserine, homo-carnosine, histidine, and aminoguanidine. The formation of AGEs was followed by fluorescence spectrophotometry at weekly intervals for 7 weeks. For the determination of the acute effect of carnosine and related compounds, HSA and collagen were incubated with 4.25% dextrose PD solutions for 24 hours, followed by incubation with 20 mmol/L of carnosine and related compounds for another 24 hours. The rate of AGE formation was monitored by fluorescence spectrophotometry. Results Carnosine and related compounds showed effective regression in AGE formation in both types of proteins in both long- and short-term exposure to PD fluids at a rate of effectiveness of the order of carnosine > homocarnosine > anserine, aminoguanidine > histidine in long-term exposure, and homocarnosine > carnosine > aminoguanidine > anserine > histidine in short-term exposure. Conclusion Carnosine and related peptides could suppress the formation of AGEs initiated by PD fluid. This observation may provide a new therapeutic approach for the prevention and treatment of the AGE-related complications in PD patients.

The activity of the rate-limiting enzyme in GSH biosynthesis, gamma-GCS, was significantly decreased in uraemic and dialysis patients, which explains, at least in part, frequent reports of reduced GSH levels in these patients. The decrease in gamma-GCS activity may have been secondary to inhibitory effects from uraemic factors that are not removed by standard dialysis. However, this assumption does not exclude the possibility of down-regulation of gamma-GCS protein expression and further studies in this context are recommended.

Background/Aims: Several studies have implicated reactive carbonyl compounds (RCOs), especially those derived from lipid peroxidation, in the development of complications frequently associated with hemodialysis (HD) treatment. However, there is still much unknown regarding the nature and concentration of RCOs in HD patients. This study was designed to evaluate the level of toxic aldehydes in the plasma of HD patients and to determine the extent to which these aldehydes contribute to RCO toxicity among these patients. Methods: 15 aldehydes of the alkanal, alkenal and 4-HO-alkenal type were measured in the plasma of 17 HD patients and 20 healthy controls. In addition, protein modification markers such as carbonyl content (CO), free thiol (SH) and residual free amino groups, as well as amyloid fibrils were also determined. Results: 11 of the 15 aldehydes were significantly elevated in the HD group when compared with the controls. Correlation studies in the HD group revealed high relationships between total alkenals plus total 4-HO-alkenals versus CO, total alkanals versus NH₂, total aldehydes versus SH, and total 4-HO-alkenals versus fibril. Conclusion: The increased levels of alkanals, alkenals and 4-HO-alkenals of lipid peroxidation in the plasma of HD patients may greatly contribute to the toxicity of RCOs. The pattern of modification of plasma protein by each group of aldehydes may provide new evidence on the in vivo mechanisms of toxicity triggered by these aldehydes on their target molecules.