imidazolone and Cataract

Aldose reductase (ALR2) inhibitors provide a viable mode to fight against diabetic complications. ALR2 exhibit plasticity in the active site vicinities and possible shifts in the nearby two supporting alpha helices. Therefore, a novel series of amino acid conjugates of chromene-3-imidazoles (13-15) were designed and synthesized based on natural isoflavonoids. The compounds were identified on the basis of spectral (

Topics: Aldehyde Reductase; Amino Acids; Animals; Benzopyrans; Blood Glucose; Catalytic Domain; Cataract; Diabetes Complications; Disease Models, Animal; Drug Design; Enzyme Activation; Enzyme Inhibitors; Imidazoles; Inhibitory Concentration 50; Molecular Docking Simulation; Rats; Stereoisomerism; Structure-Activity Relationship

To investigate whether the advanced glycation end-products (AGEs) pentosidine, N( epsilon )-(carboxymethyl)lysine (CML), and imidazolone are present in the aqueous of cataract patients and how AGE levels correlate to cataract type or the diabetic condition of the patient.. Departments of Ophthalmology and Internal Medicine, University of Jena, Jena, Germany.. Aqueous and serum samples from 77 cataractous patients (33 nondiabetics, 44 diabetics; 14 with dense posterior, 63 with nuclear cataracts) were investigated. The mean age of the patients was 69 years +/- 14 (SD). The aqueous protein concentration was examined using a laser flare-cell meter. In the samples, pentosidine was measured by high-performance liquid chromatography and CML using a competitive enzyme-linked immunosorbent assay. Western blot analysis was used to detect imidazolone, pentosidine, and CML in the aqueous.. The aqueous samples contained CML, pentosidine, or imidazolone. These AGEs occurred mainly bound to albumin. Significant correlations existed between serum pentosidine and aqueous CML and flare levels as well as between serum and aqueous CML. Patients with nuclear cataract had insignificantly higher pentosidine and CML levels than patients with posterior cataract, whereas the flare was significantly higher. No significant differences were found between the aqueous AGE levels in nondiabetic and diabetic patients.. The aqueous of cataractous eyes contained the AGEs CML, pentosidine, and imidazolone. All 3 AGEs occurred mainly albumin-bound, providing evidence they may originate from the blood. Further investigation is needed to determine the relevance of aqueous AGEs in cataractogenesis.

Topics: Aged; Albumins; Aqueous Humor; Arginine; Blotting, Western; Cataract; Chromatography, High Pressure Liquid; Electrophoresis, Polyacrylamide Gel; Female; Glycation End Products, Advanced; Humans; Imidazoles; Lysine; Male; Middle Aged; Protein Binding

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

To determine the concentrations of methylglyoxal-derived advanced glycation end-products (AGEs), the hydroimidazolones MG-H1 and -H2, in soluble human lens proteins and compare them with the concentrations of other methylglyoxal-derived AGEs and pentosidine.. Lens protein samples were hydrolyzed enzymatically. AGEs were assayed without derivatization by HPLC with tandem mass spectrometry; the fluorescent AGEs argpyrimidine and pentosidine were assayed by fluorometric detection. MG-H1 and -H2 were resolved and assayed by fluorometric detection after derivatization with 6-aminoquinolyl-N-hydroxysuccimidylcarbamate (AQC).. The methylglyoxal-derived hydroimidazolones MG-H1 and -H2 were detected and quantified in human lens proteins. AGE concentrations (mean +/- SEM) were: MG-H1 4609 +/- 411 pmol/mg protein, MG-H2 3085 +/- 328 pmol/mg protein, argpyrimidine 205 +/- 19 pmol/mg protein, and pentosidine 0.693 +/- 0.104 pmol/mg protein. The concentration of MG-H1 in human lens protein correlated positively with donor age (correlation coefficient = 0.28, P < 0.05), the concentration of MG-H2 (correlation coefficient = 0.78, P < 0.001) and argpyrimidine (correlation coefficient = 0.42, P < 0.01). The concentrations of AGEs were increased in cataractous lenses in comparison with noncataractous lenses: the increases were MG-H1 85%, MG-H2 122%, argpyrimidine 255%, and pentosidine 183% (P < 0.001). Multiple logistic regression analysis showed a significant link of cataract to donor age (regression coefficient beta = 0.094, P = 0.026) and argpyrimidine (beta = 0.022, P = 0.002).. Methylglyoxal hydroimidazolones are quantitatively major AGEs of human lens proteins. These substantial modifications of lens proteins may stimulate further glycation, oxidation, and protein aggregation leading to the formation of cataract.

Topics: Aged; Arginine; Cataract; Chromatography, High Pressure Liquid; Crystallins; Female; Fluorometry; Glycation End Products, Advanced; Humans; Hydrolysis; Imidazoles; Lens, Crystalline; Lysine; Male; Mass Spectrometry; Middle Aged; Pyruvaldehyde