imidazolone and Diabetes-Mellitus

Hemodialysis (HD) patients are frequently in a state of increased oxidative stress, and hyperglycemia appears to be a major factor. We recently found that oxidized human serum albumin (HSA) is a reliable marker of oxidative stress in HD patients. However, the issue of whether oxidized HSA is associated with the progression of oxidative stress in HD patients with or without diabetes is not clear. In the present study, we examined the effect of a qualitative modification of HSA in HD patients with or without diabetes. Blood samples from 10 HD patients with diabetes, 7 HD patients without diabetes, and 10 healthy age-matched controls were examined. The increase in plasma protein carbonyl content and advanced glycation endproducts (AGEs) in HD patients was largely due to an increase in the levels of oxidized HSA. Furthermore, these increases were greatest in HD patients with diabetes. Purified HSA from HD patients (non-DM-HSA) was carbonylated and AGE-modified. The amount of modified HSA was the highest in HD patients with diabetes (DM-HSA). Carboxy methyl lysine (CML)-modified HSA triggered a neutrophil respiratory burst, and this activity was closely correlated with the increase in the CML/HSA ratio. These findings indicate that uremia plays an important role in the progression of oxidative stress in HD patients via an increase in CML-modified HSA. They also indicate that diabetic complications further exacerbate the progression of oxidative stress by further increasing the amount of these modified HSA molecules.

Topics: Adult; Aged; Aged, 80 and over; Arginine; Blood Proteins; Case-Control Studies; Diabetes Mellitus; Female; Glycation End Products, Advanced; Humans; Imidazoles; Kidney Failure, Chronic; Lysine; Male; Middle Aged; Neutrophils; Norleucine; Oxidative Stress; Protein Carbonylation; Pyrroles; Renal Dialysis; Respiratory Burst; Serum Albumin

Chronic renal failure (CRF) is characterized by enhanced formation and accumulation of advanced glycation end products (AGEs), which are involved in the pathogenesis of vascular damage. Their role as risk factors for cardiovascular complications is still unknown. This study aims to investigate whether elevated serum levels of the AGEs pentosidine, N(epsilon)-carboxymethyllysine (CML), and the 3-deoxyglucosone-derived imidazolone involve a greater risk for cardiovascular events (CVEs) and left ventricular hypertrophy (LVH).. Patients with CRF (n = 99), on maintenance hemodialysis (HD) therapy (n = 84), and renal transplant recipients (RTRs; n = 50) were included. Pentosidine was measured by high-performance liquid chromatography, and CML and imidazolone, by enzyme-linked immunosorbent assays. Statistical analyses were performed using Mann-Whitney U test, logistic regression analysis, and Cox proportional hazards model.. At baseline in all investigated groups, patients with a history of CVEs or LVH showed greater mean serum AGE levels. By retrospective data analysis, significant odds ratios for increases in CML and imidazolone levels were calculated for LVH in HD patients, as well as for increases in CML levels for CVEs in RTRs, respectively. By prospective data analysis, serum AGE levels could not be evaluated as independent risk factors for CVEs in all investigated groups.. From these preliminary results, serum AGE levels could not be identified as independent risk factors for CVEs or LVH in patients with CRF. Prospective studies are needed to answer this question.

Topics: Adult; Aged; Aged, 80 and over; Arginine; Cardiovascular Diseases; Diabetes Mellitus; Female; Glycation End Products, Advanced; Humans; Hypertrophy, Left Ventricular; Imidazoles; Kidney Failure, Chronic; Kidney Transplantation; Lysine; Male; Middle Aged; Renal Dialysis; Retrospective Studies; Risk Factors

To investigate the occurrence of advanced glycation end products (AGEs) formed oxidatively (pentosidine and N(epsilon)-carboxymethyl lysine [CML]) or nonoxidatively (imidazolone) in human lenses and the relation of AGEs to lens coloration, cataract type, and patients' diabetic state.. Departments of Ophthalmology and Internal Medicine III, University of Jena, Jena, Germany.. Pentosidine, CML, and imidazolone concentrations were measured in the water-soluble protein fraction of 44 cataractous lenses (from 24 nondiabetic and 20 diabetic donors) and 6 noncataractous control lenses.. Pentosidine, CML, and imidazolone were higher in cataractous lenses than in control lenses (pentosidine, 3.7 pmol/mg +/- 5.3 (SD) and 1.9 +/- 1.7 pmol/mg, respectively; CML, 3.0 +/- 2.2 nmol/mg and 1.3 +/- 0.7 nmol/mg, respectively; imidazoline, 80.4 +/- 93.3 AU/mg and 19.6 +/- 18.5 AU/mg, respectively). Among the cataractous lenses, the highest AGE concentrations were found in mature cataracts, with a statistically significant increase in CML. The AGE content increased relative to the intensity of brown coloration of the lens; the brown coloration also indicated the highest rise of imidazolone compared to pentosidine and CML. Lenses from diabetic donors had generally similar pentosidine values and elevated CML and imidazolone levels compared to lenses from nondiabetic donors. The pentosidine, CML, and imidazolone levels in the lenses correlated significantly with one another but not with patient age.. Advanced glycation end products formed oxidatively and nonoxidatively occurred to a higher degree in cataractous lenses than in noncataractous lenses. The strong relationship between the lenses' AGE content, color/opacity, and the state of the cataract may indicate that advanced glycation plays a pivotal role in cataract formation.

Topics: Aged; Antibodies, Monoclonal; Arginine; Cataract; Diabetes Mellitus; Glycation End Products, Advanced; Humans; Imidazoles; Immunoenzyme Techniques; Lens, Crystalline; Lysine; Middle Aged; Oxidation-Reduction