Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells
Department of Medical Sciences, College of Pharmacy, Al-Mustansiriya University Baghdad, Iraq. Nephron Clinical Practice
(Impact Factor: 1.4).
02/2007; 107(1):c26-34. DOI: 10.1159/000106509
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.
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 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.
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.
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- "type-2 diabetic complication (Lee et al., 2005; Shi et al., 2009; Kamel et al., 2008; Tanida et al., 2004), deafness (Zhuravskii et al., 2004) and arthritis (Drafi et al., 2010) where AGEs are involved in pathology, there have been few studies where vegetarians and omnivores have been compared. It is also interesting that the presence of carnosine in heat-treated dialysis fluids has been shown to suppress deleterious AGE formation (Alhamdani et al., 2007). Carnosine is also employed commercially in eye drops to treat some forms of cataracts in humans (Barbizhayev, 2008, 2011). "
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ABSTRACT: This review will discuss the relationship between energy metabolism, protein dysfunction and the causation and modulation of age-related proteotoxicity and disease. It is proposed that excessive glycolysis, rather than aerobic (mitochondrial) activity, could be causal to proteotoxic stress and age-related pathology, due to the generation of endogenous glycating metabolites: the deleterious role of methylglyoxal (MG) is emphasized. It is suggested that TOR inhibition, exercise, fasting and increased mitochondrial activity suppress formation of MG (and other deleterious low molecular weight carbonyl compounds) which could control onset and progression of proteostatic dysfunction. Possible mechanisms by which the endogenous dipeptide, carnosine, which, by way of its putative aldehyde-scavenging activity, may control age-related proteotoxicity, cellular dysfunction and pathology, including cancer, are also considered. Whether carnosine could be regarded as a rapamycin mimic is briefly discussed.
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- "Carnosine, β-alanyl-L-histidine (L-Car) is dipeptide that was discovered in mammalian skeletal muscle (Boldyrev and Severin, 1990). Carnosine has many beneficial roles as an antioxidant (Bogardus and Boissonneault, 2000; Nagasawa et al., 2001), antiglycation molecule (Hipkiss, 2005; Alhamdani et al., 2007), anti-cross-linker (Hobart et al., 2004) and anti-aging agent (Wang et al., 2000; Hipkiss et al., 2001). Many researches on L-Car has focused on its physiological roles (Boldyrev et al., 1997; Begum et al., 2005) and therapeutic activities (Gariballa and Sinclair, 2000). "
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ABSTRACT: The objective of this research was to evaluate the effects of dietary supplementation of blood meal (BM) as a source of histidine, and magnesium oxide (MgO) as a catalyst of carnosine synthetase, on carnosine (L-Car) content in the chicken breast muscle (CBM), laying performance, and egg quality of spent old hens. Four hundred eighty laying hens (Hy-Line Brown), 95wk old, were allotted randomly into five replicates of six dietary treatments: T1; 100% basal diet, T2; 100% basal diet+MgO, T3; 97.5% basal diet+2.5% BM, T4; 97.5% basal diet+2.5% BM+MgO, T5; 95% basal diet+5% BM, T6; 95% basal diet+5% BM+MgO. Magnesium oxide was added at 0.3% of diets. The layers were fed experimental diets for 5wk. There were no significant differences in the weekly L-Car content in CBM among all treatments during the total experimental period, but some of the contrast comparisions showed higher L-Car in CBM of T6. The L-Car contents linearly decreased (p
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- "As a potent hydrophilic antioxidant, carnosine has been reported to reduce the intracellular ROS production in neuronal cells and attenuate AGEs formation in dialysis fluids. Therefore, apart from its inhibitory effect on cell cycle, it is also possible that carnosine may exert its effect via its powerful antiglycative/antioxidative pathway   . Thus, in the present study, we have demonstrated that carnosine can inhibit high-glucose-induced mesangial cell proliferation. "
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ABSTRACT: Increased mesangial cell proliferation is one of the major pathologic features in the early stage of diabetic nephropathy (DN). Carnosine is an endogenously synthesized dipeptide that has been reported as a protective factor in diabetic nephropathy. However, the underlying mechanism involved in this effect remains to be elucidated. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in cultured rat mesangial cells by the methylthiazoletetrazolium (MTT) assay, the 5-bromo-2-deoxy-uridine (BrdU) cell proliferation assay, flow cytometry and western blotting. The results showed that pretreatment of mesangial cells with carnosine significantly inhibited cell proliferation and DNA synthesis in a dose-dependent manner by increasing the cell population in G1 and reducing that in S-phase. In addition, carnosine could reverse high glucose-induced down-regulation of cyclin-dependent kinase inhibitor p21 but not that of p27. Furthermore, carnosine could reduce the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK). Taken together, these results suggest that carnosine can inhibit mesangial cell proliferation by modulating cell cycle progress, indicating that carnosine could be a potential therapeutic agent for the prevention of DN in the early stage.
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