Decreased Formation of Advanced Glycation End-Products in Peritoneal Fluid by Carnosine and Related Peptides

Abstract

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.

Serum Carnosinase-1 and Albuminuria Rather than theCNDP1Genotype Correlate with Urinary Carnosinase-1 in Diabetic and Nondiabetic Patients with Chronic Kidney Disease

“…The influence of the CNDP1 Mannheim allele has also been investigated in nondiabetic nephropathies, where it was found to be associated with a slower progression to CKD and to correlate with renal survival in patients with glomerulopathies, but not in patients with tubulointerstitial disease [22,23]. Notwithstanding the foregoing, there is compelling evidence that carnosine, a major substrate of CN-1, has renoprotective properties in animal models of diabetes [24][25][26][27]. Likewise, in human studies in patients with T2DM, carnosine supplementation has been shown to have a beneficial effect on hyperglycaemia [28,29], triglycerides, and inflammatory mediators [29].…”

Intrinsic carnosine metabolism in the human kidney

“…These dipeptides have several important protective functions. The best-characterized histidine-containing dipeptide is carnosine (Boldyrev et al 2013 ; Budzen and Rymaszewska 2013 ), which plays many roles in maintaining health, including antioxidant activity (Babizhayev et al 2013 ; Boldyrev 1993 ; Mozdzan et al 2005 ) and the ability to scavenge carbonyls (Barski et al 2013 ; Negre-Salvayre et al 2008 ; Vistoli et al 2009 ), inhibit glycation (Alhamdani et al 2007 ), and inhibit angiotensin-converting enzymes (Hou et al 2003 ; Nakagawa et al 2006 ). Carnosine also has several neuroprotective roles (Baek et al 2014 ; Boldyrev et al 2013 ; Zhang et al 2011 ).…”

Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs)

“…In contrast, endogenous transformation results from aging, uremia, and exposure to high glucose levels, such as in diabetic patients [ 5 , 6 ]. AGEs have a high renal clearance in the body, and their main pathway of elimination is through the urine (or through dialysis in case of renal function replacement) [ 9 ]. In addition, in the uremic state, increased AGEs formation is related to oxidative stress [ 10 ], which is generated by an imbalance between pro-oxidant forces (such as an increase in the ratio of oxidized glutathione to reduced glutathione) and changes in the anti-oxidant defense system (such as reduced superoxide dismutase/peroxidase activity) [ 11 ].…”