Can the introduction of an authentic learning exercise lead to the modulation of breakfast behavior in undergraduate students at University of La Réunion?

The authentic teaching and learning approach introduces real-world scenarios into the classroom to better engage Generation Z students. Considering this, we introduced an authentic learning practical exercise (breakfast meal and glycemic variation) to undergraduate biology students at the University of La Réunion (France). Here, students were initially briefed regarding the practical and subsequently determined their baseline glucose values (glucometer). They then consumed 200 mL of fruit juice together with a pain au chocolat (chocolate pastry) and subsequently recorded their glucose values at regular intervals. The last reading was done after 150 min, and they thereafter plotted such data to reveal temporal glycemic variations. During this time, the students also worked on a report to document information collected and began to supply responses to several listed questions. Three weeks after completion of the practical, we evaluated whether this intervention would lead to changes in their views regarding the nature and regularity of breakfast meal intake (employing survey questions). Our findings show that a reasonable proportion of the students indicated that the intervention did change their dietary habits, with 50% sometimes opting for an improved breakfast, whereas 10% also changed their habits albeit for only a small while. Of note, >60% of students indicated that they changed their breakfast intake habits by the end of the endocrinology module. These findings show that the beneficial effects of authentic teaching approaches may elicit relatively long-lasting changes in terms of breakfast behavioral patterns in young people and that such effects may also impact the broader society.NEW & NOTEWORTHY This study introduced an authentic learning exercise (endocrinology practical exercise) to undergraduate biology students and ascertained whether it changed their views regarding the nature and regularity of breakfast meals. Here, many altered their breakfast dietary habits, which persisted even after the completion of their module. Authentic teaching approaches can therefore trigger relatively long-lasting changes in terms of breakfast behavioral patterns in young people and may also impact the broader society.

Distribution of microglia/immune cells in the brain of adult zebrafish in homeostatic and regenerative conditions: Focus on oxidative stress during brain repair.

Microglia are macrophage-like cells exerting determinant roles in neuroinflammatory and oxidative stress processes during brain regeneration. We used zebrafish as a model of brain plasticity and repair. First, by performing L-plastin (Lcp1) immunohistochemistry and using transgenic Tg(mpeg1.1:GFP) or Tg(mpeg1.1:mCherry) fish, we analyzed the distribution of microglia/immune cells in the whole brain. Specific regional differences were evidenced in terms of microglia/immune cell density and morphology (elongated, branched, highly branched, and amoeboid). Taking advantage of Tg(fli:GFP) and Tg(GFAP::GFP) enabling the detection of endothelial cells and neural stem cells (NSCs), we highlighted the association of elongated microglia/immune cells with blood vessels and rounded/amoeboid microglia with NSCs. Second, after telencephalic injury, we showed that L-plastin cells were still abundantly present at 5 days post-lesion (dpl) and were associated with regenerative neurogenesis. Finally, RNA-sequencing analysis from injured telencephalon (5 dpl) confirmed the upregulation of microglia/immune cell markers and highlighted a significant increase of genes involved in oxidative stress (nox2, nrf2a, and gsr). The analysis of antioxidant activities at 5 dpl also revealed an upregulation of superoxide dismutase and persistent H2 O2 generation in the injured telencephalon. Also, microglia/immune cells were shown to be a source of oxidative stress at 5 dpl. Overall, our data provide a better characterization of microglia/immune cell distribution in the healthy zebrafish brain, highlighting some evolutionarily conserved features with mammals. They also emphasize that 5 days after injury, microglia/immune cells are still activated and are associated to a persistent redox imbalance. Together, these data raise the question of the role of oxidative stress in regenerative neurogenesis in zebrafish.

Metabolite Profiling of Antioxidant Rich Fractions of Punica granatum L. Mesocarp and CD36 Expression Regulation.

OBJECTIVE: It was aimed at determining which polyphenolic compound(s) in pomegranate mesocarp extract (PME) is liable for the antioxidant, anti-glycation and anti-CD36 activities. METHODS: The PME was fractionated using liquid-liquid extraction method. The fractions were tested for their polyphenolic content, antioxidant potency, anti-glycation activity and anti-CD36 potential. The metabolite compositions of PME and derived fractions were investigated in an untargeted manner using metabolomics in relation to its antioxidant and anti-glycation activities. RESULTS: The ethyl acetate and n-butanol fractions of the pomegranate mesocarp demonstrated highest antioxidant and anti-glycation potencies. These fractions, represented by gallic and ellagic acids monomers, were enriched in tannins and phenolic acids. Orthogonal partial least squares discriminate analysis (OPLS-DA) modeling of ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) metabolite profiles from the different pomegranate mesocarp fractions indicated that gallic and ellagic acids were potential contributors to the antioxidant and anti-glycation effects of the pomegranate mesocarp. At cellular level, the polyphenolic-rich crude extract as well as the ethyl acetate, n-butanol and aqueous residual fractions suppressed the protein expression of CD36. The anti-CD36 activity of these extracts and fractions was attributed to the presence of punicalagin, the ellagitannins that occurred in equal amount in the different fractions. CONCLUSION: This work demonstrated the protective effect of the non-edible part of the pomegranate fruit and showed that gallic and ellagic acids account for the antioxidant and anti-glycation activities while punicalagin is liable for the anti-CD36 activity of PME.

Methodologies and tools to shed light on erythrophagocytosis.

Red blood cells (RBC) are the most abundant circulating cell of the human body. RBC are constantly exposed to multiple stresses in the circulation, leading to molecular and structural impairments and death. The physiological process of RBC senescence or ageing is referred to as eryptosis. At the end of their lifespan, aged RBC are recognized and removed from the blood by professional phagocytes via a phenomenon called erythrophagocytosis (EP); the phagocytosis of RBC. Some genetic and acquired diseases can influence eryptosis, thereby affecting RBC lifespan and leading to hemolytic anemia. In some diseases, such as diabetes and atherosclerosis, eryptosis and EP can participate in disease progression with both professional and non-professional phagocytes. Therefore, investigating the process of EP in vivo and in vitro, as well as in different cell types, will not only contribute to the understanding of the physiological steps of EP, but also to the deciphering of the specific mechanisms involving RBC and EP that underlie certain pathologies. In this review, the process of EP is introduced and the different methods for studying EP are discussed together with examples of the experimental procedures and materials required.

Impact of Enhanced Phagocytosis of Glycated Erythrocytes on Human Endothelial Cell Functions.

Diabetes is associated with a high mortality rate due to vascular complications. Chronic hyperglycemia in diabetes leads to enhanced oxidative stress and glycation. Here, we explored the impact of glycation on human erythrocyte characteristics and capacity to affect endothelial cell function following erythrophagocytosis. Native and glucose-mediated glycated erythrocytes were prepared and characterized in terms of structural and deformability modifications. Erythrocyte preparations were tested for their binding and phagocytosis capacity as well as the potential functional consequences on human endothelial cell lines and primary cultures. Oxidative modifications were found to be enhanced in glycated erythrocytes after determination of their deformability, advanced glycation end-product content and eryptosis. Erythrophagocytosis by endothelial cells was significantly increased when incubated in the presence of glycated erythrocytes. In addition, higher iron accumulation, oxidative stress and impaired endothelial cell permeability were evidenced in cells previously incubated with glycated erythrocytes. When cultured under flow conditions, cellular integrity was disrupted by glycated erythrocytes at microvessel bifurcations, areas particularly prone to vascular complications. This study provides important new data on the impact of glycation on the structure of erythrocytes and their ability to alter endothelial cell function. Increased erythrophagocytosis may have a deleterious impact on endothelial cell function with adverse consequences on diabetic vascular complications.

Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis.

The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. This review highlights recent knowledge concerning the role of erythrocytes being more than just passive gas carriers, as potent contributors to atherosclerotic plaque progression. Erythrocyte physiology and ATH pathology is first described. Then, a specific chapter delineates the numerous links between erythrocytes and atherogenesis. In particular, we discuss the impact of extravasated erythrocytes in plaque iron homeostasis with potential pathological consequences. Hyperglycaemia is recognised as a significant aggravating contributor to the development of ATH. Then, a special focus is made on glycoxidative modifications of erythrocytes and their role in ATH. This chapter includes recent data proposing glycoxidised erythrocytes as putative contributors to enhanced atherothrombosis in diabetic patients.

Antiproliferative activity of Syzygium coriaceum, an endemic plant of Mauritius, with its UPLC-MS metabolite fingerprint: A mechanistic study.

Flowering plants from the Syzygium genus have long been used in different ethnomedicinal systems worldwide and have been under scrutiny for their biological activities. Syzygium coriaceum, an endemic plant of Mauritius has been poorly studied for its potential application against cancer. Herein, Syzygium coriaceum leaf extract has been investigated for its anticancer effect against hepatocellular carcinoma (HepG2) cells. The anticancer activity was assessed using cell proliferation assays, flow cytometry, JC-1 mitochondrial membrane potential assay, and the COMET assay. Un-targeted metabolite profiling via ultra-performance liquid chromatography coupled to high-resolution qTOF-MS (UPLC-MS) and aided by molecular networking was employed to identify the crude extract metabolites. S. coriaceum treatment induced a dose-dependent increase in lactate dehydrogenase leakage into the culture media, peaking up to 47% (p ≤ 0.0001), compared to untreated control. Moreover, at 40 µg/mL, S. coriaceum led to 88.1% (p ≤ 0.0001) drop in mitochondrial membrane potential and 5.7% (p ≤ 0.001) increased in the number of the cell population in G0/G1 phase as well as increased (p < 0.05) the proportion of cells undergoing apoptotic/necrotic cell death. More so, at 10 µg/mL, S. coriaceum induced DNA damage which was 19 folds (p < 0.001) higher than that of untreated control cells. Metabolite profiling indicated the presence of 65 metabolites, out of which 59 were identified. Tannins, flavonoids, nitrogenous compounds, and organic acids were the most predominant classes of compounds detected. Our findings showed that the presence of tannins and flavonoids in S. coriaceum leaf extract could account for the multiple mechanisms of actions underlying the antiproliferative effect against HepG2 cells.

Terminalia bentzoë, a Mascarene Endemic Plant, Inhibits Human Hepatocellular Carcinoma Cells Growth In Vitro via G0/G1 Phase Cell Cycle Arrest.

Tropical forests constitute a prolific sanctuary of unique floral diversity and potential medicinal sources, however, many of them remain unexplored. The scarcity of rigorous scientific data on the surviving Mascarene endemic taxa renders bioprospecting of this untapped resource of utmost importance. Thus, in view of valorizing the native resource, this study has as its objective to investigate the bioactivities of endemic leaf extracts. Herein, seven Mascarene endemic plants leaves were extracted and evaluated for their in vitro antioxidant properties and antiproliferative effects on a panel of cancer cell lines, using methyl thiazolyl diphenyl-tetrazolium bromide (MTT) and clonogenic cell survival assays. Flow cytometry and comet assay were used to investigate the cell cycle and DNA damaging effects, respectively. Bioassay guided-fractionation coupled with liquid chromatography mass spectrometry (MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopic analysis were used to identify the bioactive compounds. Among the seven plants tested, Terminaliabentzoë was comparatively the most potent antioxidant extract, with significantly (p < 0.05) higher cytotoxic activities. T. bentzoë extract further selectively suppressed the growth of human hepatocellular carcinoma cells and significantly halted the cell cycle progression in the G0/G1 phase, decreased the cells' replicative potential and induced significant DNA damage. In total, 10 phenolic compounds, including punicalagin and ellagic acid, were identified and likely contributed to the extract's potent antioxidant and cytotoxic activities. These results established a promising basis for further in-depth investigations into the potential use of T. bentzoë as a supportive therapy in cancer management.

Enhanced oxidative stress and damage in glycated erythrocytes.

Diabetes is associated with a dramatic mortality rate due to its vascular complications. Chronic hyperglycemia in diabetes leads to enhanced glycation of erythrocytes and oxidative stress. Even though erythrocytes play a determining role in vascular complications, very little is known about how erythrocyte structure and functionality can be affected by glycation. Our objective was to decipher the impact of glycation on erythrocyte structure, oxidative stress parameters and capacity to interact with cultured human endothelial cells. In vitro glycated erythrocytes were prepared following incubation in the presence of different concentrations of glucose. To get insight into the in vivo relevance of our results, we compared these data to those obtained using red blood cells purified from diabetics or non-diabetics. We measured erythrocyte deformability, susceptibility to hemolysis, reactive oxygen species production and oxidative damage accumulation. Altered structures, redox status and oxidative modifications were increased in glycated erythrocytes. These modifications were associated with reduced antioxidant defence mediated by enzymatic activity. Enhanced erythrocyte phagocytosis by endothelial cells was observed when cultured with glycated erythrocytes, which was associated with increased levels of phosphatidylserine-likely as a result of an eryptosis phenomenon triggered by the hyperglycemic treatment. Most types of oxidative damage identified in in vitro glycated erythrocytes were also observed in red blood cells isolated from diabetics. These results bring new insights into the impact of glycation on erythrocyte structure, oxidative damage and their capacity to interact with endothelial cells, with a possible relevance to diabetes.

Antirhea borbonica Aqueous Extract Protects Albumin and Erythrocytes from Glycoxidative Damages.

Diabetes constitutes a major health problem associated with severe complications. In hyperglycemic conditions, chronically increased oxidation and glycation of circulating components lead to advanced glycation end-products (AGEs) formation, a key contributor in diabetes complication progression. In line with literature documenting the beneficial properties of herbal teas, this study evaluates the antioxidant/glycant properties of Antirhea borbonica (Ab). Ab aqueous extract effects were tested on human albumin or erythrocytes submitted to methyl glyoxal-mediated glycoxidative damages. By using mass spectrometry, Ab aqueous extracts revealed to be rich in polyphenols. All tested biomarkers of oxidation and glycation, such as AGE, ketoamine, oxidized thiol groups, were decreased in albumin when glycated in the presence of Ab aqueous extract. Ab extract preserve erythrocyte from methylglyoxal (MGO)-induced damages in terms of restored membrane deformability, reduced oxidative stress and eryptosis phenomenon. Antioxidant capacities of Ab extract on erythrocytes were retrieved in vivo in zebrafish previously infused with MGO. These results bring new evidences on the deleterious impacts of glycation on albumin and erythrocyte in diabetes. Furthermore, it reveals antioxidant and antiglycant properties of Ab that could be used for the dietary modulation of oxidative stress and glycation in hyperglycemic situations.

Aging and glycation promote erythrocyte phagocytosis by human endothelial cells: Potential impact in atherothrombosis under diabetic conditions.

BACKGROUND AND AIMS: Atherothrombotic plaques of type 2 diabetic (T2D) patients are characterized by an increased neovascularization and intraplaque hemorrhage. The clearance of erythrocytes may be carried out by vascular cells. We explored the potential of human endothelial cells to bind and phagocyte in vitro aged and/or glycated erythrocytes as well as erythrocytes obtained from diabetic patients. METHODS: Fresh, aged and glycated-aged erythrocytes from healthy volunteers and T2D patients were tested for their binding and phagocytosis capacity as well as the potential functional consequences on endothelial cells (viability, proliferation and wound healing capacity). Immunohistochemistry was also performed in human carotid atherothrombotic samples (from patients with or without T2D). RESULTS: Aging and glycation of erythrocytes induced phosphatidylserine (PS) exposure and oxidative stress leading to enhanced endothelial cell binding and engulfment. Phagocytosis by endothelial cells was more pronounced with aged and glycated erythrocytes than with fresh ones. Phagocytosis was enhanced with T2D versus healthy erythrocytes. Furthermore, endothelial wound healing potential was significantly blunted after exposure to glycated-aged versus fresh erythrocytes. Finally, we show that interactions between erythrocytes and endothelial cells and their potential phagocytosis may occur in vivo, in atherothrombotic conditions, in neovessels and in the luminal endothelial lining. CONCLUSIONS: Endothelial cells may play an important role in erythrocyte clearance in an atherothrombotic environment. Under diabetic conditions, erythrocyte glycation favors their engulfment by endothelial cells and may participate in endothelial dysfunction, thereby promoting vulnerable atherothrombotic plaques to rupture.

Glycation of human serum albumin impairs binding to the glucagon-like peptide-1 analogue liraglutide.

The long-acting glucagon-like peptide-1 analogue liraglutide has proven efficiency in the management of type 2 diabetes and also has beneficial effects on cardiovascular diseases. Liraglutide's protracted action highly depends on its capacity to bind to albumin via its palmitic acid part. However, in diabetes, albumin can undergo glycation, resulting in impaired drug binding. Our objective in this study was to assess the impact of human serum albumin (HSA) glycation on liraglutide affinity. Using fluorine labeling of the drug and 19F NMR, we determined HSA affinity for liraglutide in two glycated albumin models. We either glycated HSA in vitro by incubation with glucose (G25- or G100-HSA) or methylglyoxal (MGO-HSA) or purified in vivo glycated HSA from the plasma of diabetic patients with poor glycemic control. Nonglycated commercial HSA (G0-HSA) and HSA purified from plasma of healthy individuals served as controls. We found that glycation decreases affinity for liraglutide by 7-fold for G100-HSA and by 5-fold for MGO-HSA compared with G0-HSA. A similarly reduced affinity was observed for HSA purified from diabetic individuals compared with HSA from healthy individuals. Our results reveal that glycation significantly impairs HSA affinity to liraglutide and confirm that glycation contributes to liraglutide's variable therapeutic efficiency, depending on diabetes stage. Because diabetes is a progressive disease, the effect of glycated albumin on liraglutide affinity found here is important to consider when diabetes is managed with this drug.

Extracts of Mauritian Carica papaya (var. solo) protect SW872 and HepG2 cells against hydrogen peroxide induced oxidative stress.

In line with literature documenting the pluripotent activities of tropical fruits, this study evaluated the antioxidant effects of Carica papaya fruit extracts at cellular level. Investigations using cellular models of oxidative stress provided complementary evidence of the antioxidant activities of papaya fruit. At 2 mg dry weight ml-1, extracts of seed from ripe and unripe fruit significantly reduced oxidative stress levels within human pre-adipocytes (SW872) and hepatocellular carcinoma cells (HepG2) exposed to hydrogen peroxide (H2O2). Maintenance of mitochondrial viability, reduction of intracellular reactive oxygen species levels and mediation of pro-inflammatory cytokine secretory levels (tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1) were all indicative of its cytoprotective effects against oxidative-inflammation. This work demonstrates that the Mauritian Solo papaya is an important source of natural antioxidants that could be used for the dietary modulation of oxidative stress and inflammation.

Glycated human albumin alters mitochondrial respiration in preadipocyte 3T3-L1 cells.

Diabetes and obesity are strongly associated with increased levels of circulating advanced glycation end products (AGEs) and reactive oxygen species (ROS). These two molecular phenomena affect the physiology of adipose tissue, a biological driver of the metabolic syndrome, leading to an inflammatory profile and insulin resistance, which could contribute to obesity/diabetes-associated complications, such as cardiovascular diseases. Herein, we investigated the impact of AGEs on mitochondrial bioenergetics in murine preadipocyte cells (3T3-L1) and cellular redox homeostasis. We show that incubation of preadipocytes with AGEs stimulates mitochondrial activity and respiration while inducing oxidative stress. This AGE-induced intracellular ROS production was blocked by diphenylene iodonium, an NAD(P)H oxidase inhibitor. In parallel, antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were found to be activated upon AGE treatment. Our results suggest that AGE-induced oxidative stress is generated by NAD(P)H oxidase and leads to a cellular proliferation arrest associated with enhanced mitochondrial metabolism and biogenesis, and with increased levels of ROS-detoxifying enzymes, as well. These new data show how AGEs may be involved in hyperglycemia-induced oxidative damage in preadipocytes and their potential links to diabetes progression. © 2017 BioFactors, 43(4):577-592, 2017.

Lactic Fermentation as an Efficient Tool to Enhance the Antioxidant Activity of Tropical Fruit Juices and Teas.

Tropical fruits like pineapple, papaya, mango, and beverages such as green or black teas, represent an underestimated source of antioxidants that could exert health-promoting properties. Most food processing technologies applied to fruit beverages or teas result in an impairment of inherent nutritional properties. Conversely, we hypothesise that lactic acid fermentation may constitute a promising route to maintain and even improve the nutritional qualities of processed fruits. Using specific growth media, lactic acid bacteria were selected from the fruit phyllosphere diversity and fruit juice, with the latter undergoing acidification kinetics analyses and characterised for exopolysaccharide production. Strains able to ferment tropical fruit juices or teas into pleasant beverages, within a short time, were of particular interest. Strains Weissella cibaria 64 and Leuconostoc mesenteroides 12b, able to increase antioxidant activity, were specifically studied as potential starters for lactic fermented pineapple juice.

Glycation abolishes the cardioprotective effects of albumin during ex vivo ischemia-reperfusion.

Hyperglycemia-induced oxidative stress plays a key role in the onset/progression of cardiovascular diseases. For example, it can trigger formation of advanced glycation end (AGE) products with ischemia-reperfusion performed under hyperglycemic conditions. For this study, we hypothesized that albumin modified by glycation loses its unique cardioprotective properties in the setting of ischemia-reperfusion under high glucose conditions. Here, ex vivo rat heart perfusions were performed under simulated normo- and hyperglycemic conditions, that is Krebs-Henseleit buffer containing 11 mmol/L and 33 mmol/L glucose, respectively, ± normal or glycated albumin preparations. The perfusion protocol consisted of a 60 min stabilization step that was followed by 20 min of global ischemia and 60 min reperfusion. Additional experiments were completed to determine infarct sizes in response to 20 min regional ischemia and 120 min reperfusion. At the end of perfusions, heart tissues were isolated and evaluated for activation of the AGE pathway, oxidative stress, and apoptosis. Our data reveal that native bovine serum albumin treatment elicited cardioprotection (improved functional recovery, decreased infarct sizes) under high glucose conditions together with enhanced myocardial antioxidant capacity. However, such protective features are lost with glycation where hearts displayed increased infarct sizes and poor functional recovery versus native albumin treatments. Myocardial antioxidant capacity was also lowered together with activation of the intracellular AGE pathway. These data therefore show that although albumin acts as a cardioprotective agent during ischemia-reperfusion, it loses its cardioprotective and antioxidant properties when modified by glycation.

Impaired constitutive and regenerative neurogenesis in adult hyperglycemic zebrafish.

A growing body of evidence supports hyperglycemia as a putative contributor to several brain dysfunctions observed in diabetes patients, such as impaired memory capacity, neural plasticity, and neurogenic processes. Thanks to the persistence of radial glial cells acting as neural stem cells, the brain of the adult zebrafish constitutes a relevant model to investigate constitutive and injury-induced neurogenesis in adult vertebrates. However, there is limited understanding of the impact of hyperglycemia on brain dysfunction in the zebrafish model. This work aimed at exploring the impact of acute and chronic hyperglycemia on brain homeostasis and neurogenesis. Acute hyperglycemia was shown to promote gene expression of proinflammatory cytokines (il1ß, il6, il8, and tnfα) in the brain and chronic hyperglycemia to impair expression of genes involved in the establishment of the blood-brain barrier (claudin 5a, zona occludens 1a and b). Chronic hyperglycemia also decreased brain cell proliferation in most neurogenic niches throughout the forebrain and the midbrain. By using a stab wound telencephalic injury model, the impact of hyperglycemia on brain repair mechanisms was investigated. Whereas the initial step of parenchymal cell proliferation was not affected by acute hyperglycemia, later proliferation of neural progenitors was significantly decreased by chronic hyperglycemia in the injured brain of fish. Taken together, these data offer new evidence highlighting the evolutionary conserved adverse effects of hyperglycemia on neurogenesis and brain healing in zebrafish. In addition, our study reinforces the utility of zebrafish as a robust model for studying the effects of metabolic disorders on the central nervous system. J. Comp. Neurol. 525:442-458, 2017. © 2016 Wiley Periodicals, Inc.

Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated albumin.

Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively. Our data reveal increased oxidative stress biomarkers and lipid accumulation in plasma and livers of diabetic mice, together with albumin glycoxidation. Purified mouse albumin modifications resembled those typically found in diabetic patients, i.e. degree of glycation, carbonylation, AGE levels and in terms of chemical composition. Receptor for AGE expression and reactive oxygen species production were upregulated in db/db mouse livers, together with impaired proteolytic, antioxidant and mitochondrial respiratory activities. In parallel, acute exposure of HepG2 cells to glycated albumin also elicited intracellular free radical formation. Together this study demonstrates that AGE-modified albumin can trigger damaging effects on the liver, i.e. by increasing oxidative stress, attenuating antioxidant capacity, and by impairment of hepatic proteolytic and respiratory chain enzyme activities.

Association between Fluorescent Advanced Glycation End-Products and Vascular Complications in Type 2 Diabetic Patients.

OBJECTIVES: Diabetes is a major health problem associated with hyperglycemia and chronically increased oxidative stress and enhanced formation of advanced glycation end-products (AGEs). The aim of this study was to determine whether oxidative plasma biomarkers in diabetic patients could be evidenced and associated with vascular complications. METHODS: Oxidative stress biomarkers such as thiols, ischemia-modified albumin (IMA), glycated albumin (GA), fructosamine, and AGEs were measured in 75 patients with poorly controlled type 2 diabetes (HbA1c > 7.5%) with (44) or without (31) vascular disease and in 31 nondiabetic controls. RESULTS: Most biomarkers of oxidation and glycation were significantly increased in diabetic patients in comparison with nondiabetics. Fructosamines, GA, IMA, and AGEs were positively correlated and levels of fluorescent AGEs were significantly increased in the plasma from patients presenting vascular complication. CONCLUSIONS: These results bring new evidence for the potential interest of glycated albumin, oxidative stress, and glycoxidation parameters in the monitoring of type 2 diabetic patients. Furthermore, it emphasizes fluorescent AGEs as a putative indicator for vascular event prediction in diabetic patients.