muramidase and 3-deoxyglucose

It has been hypothesized that advanced Maillard reaction in vivo could explain some of the age- and diabetes-related changes. Furthermore, involvement of the Maillard reaction with Alzheimer's disease has also been suggested, as advanced glycation end products, such as pyrraline and pentosidine, were demonstrated to localize in lesions of the disease. Although aminoguanidine has been studied extensively and established as an inhibitor of the Maillard reaction, other candidates have not been investigated thoroughly. In the present study, we examined the inhibitory effect of tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone], an antidementia drug, on the Maillard reaction. Tenilsetam inhibited glucose- and fructose-induced polymerization of lysozyme in a concentration-dependent manner in vitro. Reduced enzymatic digestibility of collagen incubated with 100 mM glucose for 4 weeks was also restored to a control level by coincubation with 100 mM tenilsetam. To determine whether tenilsetam inhibits the Maillard reaction in vivo, streptozotocin-induced diabetic rats were treated with tenilsetam (50 mg/kg x day). Elevated levels of advanced glycation end-product-derived fluorescence and pyrraline in renal cortex and aorta of diabetic rats were suppressed by the administration of tenilsetam for 16 weeks. These inhibitory effects of this agent on advanced glycation in diabetic rats suggested its potential therapeutic role in controlling diabetic complications.

Topics: Animals; Aorta; Blood Glucose; Collagen; Deoxyglucose; Diabetes Mellitus, Experimental; Fructose; Glucose; Glycated Hemoglobin; Kidney Cortex; Macromolecular Substances; Maillard Reaction; Male; Muramidase; Norleucine; Piperazines; Psychotropic Drugs; Pyrroles; Rats; Rats, Sprague-Dawley; Spectrometry, Fluorescence; Thiophenes

The generation of fluorescence and 3-deoxyglucosone (3DG), browning, polymerization, and impairment of the amino acid residues of lysozyme incubated with glucose were investigated at 37 degrees C and 50 degrees C at pH 7.4 in a phosphate or TAPSO buffer under aerobic and non-aerobic conditions with or without DETAPAC as a chelating reagent. Browning, the generation of fluorescence, and polymerization were accelerated under the non-aerobic, compared to aerobic, conditions. Moreover, the formation of 3DG was also significantly increased under non-aerobic conditions. The incubation of both reaction systems resulted in noticeable losses of arginine and lysine residues. DETAPAC significantly inhibited the advanced Maillard reaction under both aerobic and non-aerobic conditions. However, DETAPAC had no effect on the impairment of lysine and arginine residues. The generation of fluorescence, browning and polymerization of lysozyme in the TAPSO buffer were markedly inhibited under both aerobic and non-aerobic conditions. These observations suggest that transition metals in the phosphate buffer may have accelerated the formation of Amadori compounds via Schiff's base. In addition, under non-aerobic conditions, the formation of advanced glycation end products from 3DG via Amadori compounds is presumed to be the major pathway, because the formation of N epsilon-(carboxymethyl)lysine, glyoxal, and glucosone was accelerated by an oxidative reaction catalyzed with transition metal ions. These presumptions are supported by the results from a lysozyme-3DG reaction system.

Topics: Aerobiosis; Amino Acids; Chelating Agents; Chemical Phenomena; Chemistry, Physical; Deoxyglucose; Electrophoresis, Polyacrylamide Gel; Glucose; Indicators and Reagents; Maillard Reaction; Metals; Muramidase; Oxygen; Pentetic Acid; Spectrometry, Fluorescence