Total Advanced Glycation End-products Research Articles

Hemodialysis biomarkers: total advanced glycation end products (AGEs) against oxidized human serum albumin (HSAox).

Nephropathic patients show higher levels of advanced glycation end products (AGEs) and oxidized human serum albumin (HSAox) compared to healthy subjects. These two classes of compounds are formed as the result of oxidative insults; for this reason, they can be useful oxidative stress biomarkers. The present study examines the variation of AGEs and HSAox in hemodialysis (HD) patients before and after dialysis session, evaluating the impact of different dialytic techniques and filters on their removal. A total of 50 healthy subjects (control group) and 130 HD patients were enrolled in the study. Hemodialysis patients were subdivided based on dialytic techniques: 109 in diffusive technique and 22 in convective technique. We monitored HSAox, AGEs and other laboratory parameters at early morning in healthy subjects and in HD patients before and after the dialysis procedures. The level of HSAox decreases after a single dialytic session (from 58.5 ± 8.8% to 41.5 ± 11.1%), but the concentration of total AGEs increases regardless of adopted dialytic techniques (from 6.8 ± 5.2µg/ml to 9.2 ± 4.4µg/ml). In our study, levels of HSAox and total AGEs are similar in diabetic and non-diabetic HD patients. The increase in total AGEs after dialysis was only observed using polysulfone filters but was absent with polymethacrylate filters. HSAox is a simple and immediate method to verify the beneficial effect of a single dialysis session on the redox imbalance, always present inHD patients. Total AGEs assayed by ELISA procedure seem to be a less reliable biomarker in this population.

In vitro and in vivo inhibition of aldose reductase and advanced glycation end products by phloretin, epigallocatechin 3-gallate and [6]-gingerol.

Hyperglycemic stress activates polyol pathway and aldose reductase (AR) key enzyme responsible for generating secondary complications during diabetes. In this study the therapeutic potential of phloretin, epigallocatechin 3-gallate (EGCG) and [6]-gingerol were evaluated for anti-glycating and AR inhibitory activity in vitro and in vivo systems. Human retinal pigment epithelial (HRPE) cells were induced with high glucose supplemented with the phloretin, EGCG and [6]-gingerol. Aldose reductase activity, total advanced glycation end products (AGEs) and enzyme inhibitor kinetics were assessed. Male C57BL/6J mice were randomly assigned to one of the different treatments (bioactive compounds at 2 concentrations each) with either a low fat diet or high fat diet (HFD). After sixteen weeks, AGE accumulation and AR activity was determined in heart, eyes and kidney. High glucose induced toxicity decreased cell viability compared to the untreated cells and AR activity increased to 2-5 folds from 24 to 96h. Pre-treatment of cells with phloretin, EGCG and [6]-gingerol improved cell viability and inhibited AR activity. The enzyme inhibition kinetics followed a non-competitive mode of inhibition for phloretin and EGCG whereas [6]-gingerol indicated uncompetitive type of inhibition against AR. Data from the animal studies showed high plasma glucose levels in HFD group over time, compared to the low fat diet. HFD group developed cataract and AR activity increased to 4 folds compared to the group with low fat diet. Administration of EGCG, phloretin and [6]-gingerol significantly reduced blood sugar levels, AGEs accumulation, and AR activity. These findings could provide a basis to consider using the selected dietary components alone or in combination with other therapeutic approaches to prevent diabetes-related complications in humans.

Pilot study: Hypoglycemic and antiglycation activities of bitter melon (Momordica charantia L.) in type 2 diabetic patients

Background/ObjectivesBitter melon (Momordica charantia L., MC) has been used as a traditional remedy in diabetics due to its hypoglycemic activity. However, its anti-hyperglycemic effect and antiglycation activity have been demonstrated in vitro and in animal experiments, but not in a long-term clinical study. The aim of this study was to investigate the effect of bitter melon on long-term glycemic control and glycation status in type 2 diabetic patients. MethodsThis study was a two-arm, parallel, randomized, double-blinded, placebo-controlled trial in which type 2 diabetic patients were randomized to continuously take either 6 g/day of MC dried-fruit pulp containing 6.26 ± 0.28 mg of charantin (N = 19) or placebo (N = 19) for 16 weeks. ResultsAfter 8 and 16 weeks of the treatment, the reduction of A1C from baseline in the MC group was greater than that of the placebo group (0.25 ± 0.12%, P = 0.042 and 0.31 ± 0.15%, P = 0.044, respectively). In addition, the MC group showed a significant decline of total advanced glycation endproducts (AGEs) in serum after 16 weeks of the intervention. The mean difference between both groups was 8.22 ± 3.58 × 103 AU/g protein (P = 0.028). The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum creatinine (Cr) did not change from baseline in each group and were not different between the two groups. None of participants experienced serious adverse events. ConclusionsIt is possible that this herb is beneficial not only on glycemic control, but also on potential systemic complications of type 2 diabetes mellitus.

Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell's mole-rat (Fukomys anselli).

Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.

Inhibitory effects of microalgal extracts on the formation of advanced glycation endproducts (AGEs)

The antiglycative activities of 20 microalgae at different growth phases were evaluated for the first time. In a bovine serum albumin (BSA)-glucose system, ethyl acetate fractions of green microalgae Chlorella and diatom Nitzschia laevis exhibited the highest inhibitory effects against the formation of total advanced glycation endproducts (AGEs) (inhibition rates: 81.76–88.02% and 91.68%) at the concentration of 500 ppm. Such abilities were higher than the effect of 1 mM aminoguanidine (AG) solution (inhibition rate: 80.51%), a commonly used inhibitor of glycation process. In addition to total AGEs, these fractions were also found to be effective in the blockage of the formation of two specific AGEs, pentosidine and N ε -Carboxymethyllysine (CML). Different from many other plant species, AGE inhibitory abilities of selected microalgae were not due to the presence of phenolic compounds. HPLC and gas chromatography (GC) analysis revealed that carotenoids in Chlorella and unsaturated fatty acids, mainly of linoleic acid, arachidonic acid and eicosapentaenoic acid in Nitzschia laevis contributed to their strong antiglycative capacities.