Serum albumin and cardiovascular disease: State-of-the-art review.

Cardiovascular disease is the leading cause of death worldwide. Conceptually, endothelial dysfunction, inflammatory conditions and oxidative stress are at the forefront of the onset and development of most cardiovascular diseases, particularly coronary artery disease and heart failure. Serum albumin has many physiological properties, including in particular antioxidant, anti-inflammatory, anticoagulant and anti-platelet aggregation activity. It also plays an essential role in the exchange of fluids across the capillary membrane. Hypoalbuminemia is a powerful prognostic marker in the general population as well as in many disease states. In the more specific context of cardiovascular disease, low serum albumin is independently associated with the development of various deleterious conditions such as coronary artery disease, heart failure, atrial fibrillation, stroke and venous thromboembolism. Low serum albumin has also emerged as a potent prognostic parameter in patients with cardiovascular disease regardless of usual prognostic markers. Remarkably, its potent prognostic value persists after adjusting for causative confounders such as malnutrition and inflammation. This prognostic value probably refers primarily to the syndrome of malnutrition-inflammation and the severity of comorbidities. Nevertheless, several recent meta-analyses strongly support the hypothesis that hypoalbuminemia may act as an unrecognized, potentially modifiable risk factor contributing to the emergence and progression of cardiovascular disease, primarily by exacerbating oxidative stress, inflammation and platelet aggregation, and by favouring peripheral congestion and pulmonary edema. Currently, it is unknown whether prevention and correction of low serum albumin offers a benefit to patients with or at risk for cardiovascular disease, and further studies are critically needed in this setting.

Investigating the Impact of Albumin on the Liver Uptake of Pitavastatin and Warfarin in Nagase Analbuminemic Rats.

Albumin has been suggested to enhance the hepatic uptake of organic anion-transporting polypeptide (Oatp) substrates in various in vitro as well as liver perfusion models. However, it is not known whether the interplay between albumin and Oatp substrates is an experimental artifact or if this interaction occurs in vivo. The objective of this work was to investigate the hepatic uptake of warfarin and pitavastatin, which are both extensively bound to albumin but only pitavastatin being an Oatp substrate. Experiments were conducted in Nagase analbuminemic rats (NAR) which exhibit reduced albumin levels compared with F344 (wild type, WT). The fraction unbound (f u) was 140- and 10-fold greater in NAR plasma for warfarin and pitavastatin, respectively, whereas no meaningful differences were observed with tissue binding. In vitro, pitavastatin uptake into hepatocytes reconstituted in WT plasma was 17- and 3-fold greater than when reconstituted in buffer or NAR plasma, respectively. In vivo, the free tissue-to-free plasma ratios (K p,u,u) from brain and liver in intact WT and NAR were not significantly different for warfarin. Contrarily, liver K p,u,u of pitavastatin was 6-fold higher in WT animals, which corresponded to a 2.3-fold reduction in free plasma and 2.6-fold increase in free liver exposure. These results suggest that the enhanced hepatic uptake by albumin is not necessarily an experimental artifact but is also a relevant phenomenon in vivo. This work raises the possibility that other plasma proteins may also effect the function of additional drug transporters, and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs. SIGNIFICANCE STATEMENT: The interplay between albumin and Oatp substrates has been reported in hepatocytes and in liver perfusion studies, but the in vivo relevance of this interaction has yet to be elucidated. Using NAR and its corresponding WT animal, this study demonstrates that albumin may indeed enhance the hepatic uptake of pitavastatin in intact animals. In vivo demonstration of this interplay not only provides further justification for continued investigation into this particular mechanism but also raises the possibility that other plasma proteins may affect additional drug transporters and that modulating plasma protein binding may exhibit meaningful clinical relevance in the disposition of drugs.

Albumin mass balance and kinetics in liver transplantation.

BACKGROUND: In major abdominal surgery albumin is shifted from the circulation, presumably leaking into the interstitial space, contributing to a 30-40% decrease in plasma albumin concentration. During and after liver transplantation exogenous albumin is infused for volume substitution and to maintain plasma albumin concentration. Here we used liver transplantation as a model procedure for the study of albumin mass balance and kinetics during major abdominal surgery with albumin substitution. METHODS: Patients were studied during liver transplantation (n = 16), and until postoperative day 3 (POD 3) (n = 11). Cumulative perioperative albumin shift was assessed by mass balance of albumin and hemoglobin. Synthesis rates of albumin and fibrinogen were estimated by the flooding technique using deuterium-labeled phenylalanine. Albumin distribution was assessed by radioiodinated human serum albumin. RESULTS: At the end of surgery, 37 ± 17 g of albumin (p < 0.0001) had shifted from plasma, and this amount was stable until POD 3 (48 ± 33 g, p = 0.0017 versus baseline). There was 91 ± 37 g exogenous albumin infused peroperatively and another 47 ± 35 g was infused postoperatively until POD 3. Absolute synthesis rates of albumin and fibrinogen on POD 3 were 239 ± 84 mg/kg body weight/day and 33 mg/kg body weight/day (range 5-161), respectively. CONCLUSIONS: Albumin net leakage from plasma progressed until the end of surgery, and was then unaltered until POD 3. This is in contrast with the normalization of the cumulative albumin shift identified at day 3 after non-transplant major abdominal surgery. Liver synthesis of export proteins was high compared to reference values at the third postoperative day, suggesting rapid recovery of synthesis capacity. TRIAL REGISTRATION: Swedish Medical Product Agency, EudraCT 2015-002568-18. Registered on 15 July 2015.

Do glycoalbumin levels preferentially reflect changes in postprandial glucose excursions?

AIMS: To evaluate whether plasma glycated albumin, which provides an integrated measure of plasma glucose levels over the preceding 2-4 weeks, better reflects changes in postprandial glucose excursions than HbA1c . METHODS: People with suboptimum glycaemic control on dual oral therapy were enrolled in the Treating-to-Target-in-Type 2 diabetes (4-T) trial, in which participants were randomized to the addition of once-daily basal insulin, twice-daily biphasic insulin or thrice-daily prandial insulin. Glycated albumin levels were assayed enzymatically from baseline and 1-year fasting plasma samples. We evaluated robust correlations of glycated albumin and HbA1c both with fasting and postprandial glucose levels at these two time points, and with insulin-induced changes in the postprandial excursion. RESULTS: Requisite data were available for 625 of the participants in the 4-T trial. Their mean (±sd) age was 62 ± 10 years and body weight was 85.8 ± 15.9 kg, and their median (interquartile range) diabetes duration was 9 (6, 13) years. Partial correlations at baseline and 1 year between postprandial glucose excursions and glycated albumin/HbA1c , after adjusting for fasting glucose, were 0.27/0.15 and 0.22/0.18, respectively. Glycated albumin, compared with HbA1c , explained 66% more of the variation in postprandial glucose excursions at baseline. At 1 year, postprandial glucose excursions on basal, biphasic and prandial and insulin therapy were reduced by 0.43, 0.78 and 1.88 mmol/l, respectively. These reductions were associated with changes in both glycated albumin and HbA1c (P < 0.01), with a stronger association for glycated albumin. CONCLUSION: Changes in glycated albumin and HbA1c reflect changes in postprandial glucose excursions to a similar extent.

Evaluation of glycated albumin (GA) and GA/HbA1c ratio for diagnosis of diabetes and glycemic control: A comprehensive review.

Diabetes Mellitus (DM) is a group of metabolic diseases characterized by chronic high blood glucose concentrations (hyperglycemia). When it is left untreated or improperly managed, it can lead to acute complications including diabetic ketoacidosis and non-ketotic hyperosmolar coma. In addition, possible long-term complications include impotence, nerve damage, stroke, chronic kidney failure, cardiovascular disease, foot ulcers, and retinopathy. Historically, universal methods to measure glycemic control for the diagnosis of diabetes included fasting plasma glucose level (FPG), 2-h plasma glucose (2HP), and random plasma glucose. However, these measurements did not provide information about glycemic control over a long period of time. To address this problem, there has been a switch in the past decade to diagnosing diabetes and its severity through measurement of blood glycated proteins such as Hemoglobin A1c (HbA1c) and glycated albumin (GA). Diagnosis and evaluation of diabetes using glycated proteins has many advantages including high accuracy of glycemic control over a period of time. Currently, common laboratory methods used to measure glycated proteins are high-performance liquid chromatography (HPLC), immunoassay, and electrophoresis. HbA1c is one of the most important diagnostic factors for diabetes. However, some reports indicate that HbA1c is not a suitable marker to determine glycemic control in all diabetic patients. GA, which is not influenced by changes in the lifespan of erythrocytes, is thought to be a good alternative indicator of glycemic control in diabetic patients. Here, we review the literature that has investigated the suitability of HbA1c, GA and GA:HbA1c as indicators of long-term glycemic control and demonstrate the importance of selecting the appropriate glycated protein based on the patient's health status in order to provide useful and modern point-of-care monitoring and treatment.

The relationship between serum albumin levels and 24-h ambulatory blood pressure monitoring recordings in non-diabetic essential hypertensive patients.

OBJECTIVES: The goal of this study was to evaluate the relationship between serum albumin levels and 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings in non-diabetic essential hypertensive patients. METHODS: A total of 354 patients (mean [SD] age: 55.5 [14.3] years, 50% females) with essential hypertension and 24-h ABPM recordings were included. Patient 24-h nighttime and daytime ABPM values, systolic and diastolic dipping status and average nocturnal dipping were recorded. The correlations between serum albumin levels and nocturnal systolic and diastolic dipping were evaluated, and correlates of average nocturnal systolic dipping were determined via a linear regression model. RESULTS: Overall, 73.2% of patients were determined to be non-dippers. The mean (SD) levels of serum albumin (4.2 [0.3] g/dL vs. 4.4 [0.4] g/dL, p<0.001) and the average nocturnal systolic (15.2 [4.8] mmHg vs. 0.3 [6.6] mmHg, p<0.001) and diastolic dipping (4.2 [8.6] mmHg vs. 18.9 [7.0] mmHg, p<0.001) were significantly lower in non-dippers than in dippers. A significant positive correlation was noted between serum albumin levels and both systolic (r=0.297, p<0.001) and diastolic dipping (r=0.265, p<0.001). The linear regression analysis revealed that for each one-unit increase in serum albumin, the average nocturnal dip in systolic BP increased by 0.17 mmHg (p=0.033). CONCLUSION: Our findings indicate an association between serum albumin levels and the deterioration of circadian BP rhythm among essential hypertensive patients along with the identification of a non-dipper pattern in more than two-thirds of patients. Our findings emphasize the importance of serum albumin levels, rather than urinary albumin excretion, as an independent predictor of nocturnal systolic dipping, at least in non-diabetic essential hypertensive patients with moderate proteinuria.

The relationship between serum albumin levels and 24-h ambulatory blood pressure monitoring recordings in non-diabetic essential hypertensive patients

OBJECTIVES: The goal of this study was to evaluate the relationship between serum albumin levels and 24-hour ambulatory blood pressure monitoring (24-h ABPM) recordings in non-diabetic essential hypertensive patients. METHODS: A total of 354 patients (mean [SD] age: 55.5 [14.3] years, 50% females) with essential hypertension and 24-h ABPM recordings were included. Patient 24-h nighttime and daytime ABPM values, systolic and diastolic dipping status and average nocturnal dipping were recorded. The correlations between serum albumin levels and nocturnal systolic and diastolic dipping were evaluated, and correlates of average nocturnal systolic dipping were determined via a linear regression model. RESULTS: Overall, 73.2% of patients were determined to be non-dippers. The mean (SD) levels of serum albumin (4.2 [0.3] g/dL vs. 4.4 [0.4] g/dL, p<0.001) and the average nocturnal systolic (15.2 [4.8] mmHg vs. 0.3 [6.6] mmHg, p<0.001) and diastolic dipping (4.2 [8.6] mmHg vs. 18.9 [7.0] mmHg, p<0.001) were significantly lower in non-dippers than in dippers. A significant positive correlation was noted between serum albumin levels and both systolic (r=0.297, p<0.001) and diastolic dipping (r=0.265, p<0.001). The linear regression analysis revealed that for each one-unit increase in serum albumin, the average nocturnal dip in systolic BP increased by 0.17 mmHg (p=0.033). CONCLUSION: Our findings indicate an association between serum albumin levels and the deterioration of circadian BP rhythm among essential hypertensive patients along with the identification of a non-dipper pattern in more than two-thirds of patients. Our findings emphasize the importance of serum albumin levels, rather than urinary albumin excretion, as an independent predictor of nocturnal systolic dipping, at least in non-diabetic essential hypertensive patients with moderate proteinuria.

Aging-associated oxidized albumin promotes cellular senescence and endothelial damage.

Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.

[Effect of Human Serum Albumin on Endotoxin Scattering Photometry].

PURPOSE: Laser scattering photometry (ESP) is a newly developed plasma endotoxin assay method using horseshoe crab amebocyte lysate (AL) that recognizes small particles produced by polymerization of coagulin under the stirring conditions at 1000rpm. We elucidated the effect of human serum album (HSA) in the ESP method. METHODS: AL was dissolved with 630µL of the specimen and a 200-µL aliquot was used for ESP; this conventional protocol was regarded as the ESP630 method. The ESP210 method was also used, i. e. AL was dissolved with 210µL of the specimen and a 200-µL aliquot was used for ESP. RESULTS: Water induced the agglutination, and HSA prolonged the agglutination time depending on its concentration especially in the ESP630 method. The water-induced agglutination was not inhibited by the addition of anti-factor C monoclonal antibody, and amidinophenyl benzoate hydrochloride, used as a clotting enzyme inhibitor, intensively inhibited the water-induced agglutination. Therefore, the water-induced agglutination was suggested to be a false-positive reaction to non-specific activation of the clotting enzyme. The HSA-induced prolongation of the reaction in the national health insurance-covered turbidimetric kinetic assay was not observed. CONCLUSION: HSA or plasma protein seemed to affect the result, especially in the ESP630 method, and a non-specific reaction was found to occur in the ESP methods.

OSSC1E-K19, a novel phytochemical component of Osteomeles schwerinae, prevents glycated albumin-induced retinal vascular injury in rats.

In the pathophysiology of diabetic retinopathy (DR), advanced glycation end products (AGEs) and vascular endothelial growth factor (VEGF) are thought to have important roles. It is known that VEGF causes a breakdown of the blood­retinal barrier (BRB) and retinal neovascularization; however, how AGEs affect the retina has largely remained elusive. OSSC1E­K19 is a novel phytochemical component of Osteomeles schwerinae. The objective of the present study was to evaluate the protective effects of OSSC1E­K19 on retinal vascular injury in AGE­modified rat serum albumin (AGE-RSA)-induced retinopathy. AGE-RSA-injected rat eyes were used investigate the protective effects of OSSC1E­K19 on BRB breakdown. Intravitreal injection of OSSC1E-K19 prevented AGE-RSA-induced BRB breakdown and decreased retinal VEGF expression in retinal vessels. In addition, OSSC1E-K19 inhibited the loss of occludin, a significant tight junction protein. These results supported the potential therapeutic utility of OSSC1E-K19 for retinal vascular permeability diseases.

What could be the role of molecular-based allergy diagnostics in detecting the risk of developing allergic sensitization to furry animals?

Although this highly refined diagnostic approach has been used in several fields of allergy diagnosis, we noticed the scarcity of data on the role of CDR in detecting current sensitization to the allergens of common pets (cat / dog) and, especially, its potential usefulness in predicting the risk of sensitization to other furry animals. Reported data suggest that cross-reacting mechanisms might play an important role in a significant proportion of allergic sensitizations to furry animals (common pets and unusual / exotic mammals) especially in the absence of any possible direct / indirect contact. In this context an evaluation of specific IgE by using the micro-array technique ImmunoCAP ISAC (Thermofisher Scientific - Immuno-Diagnostics, Sweden) for lipocalins (Can f 1, Can f 2, Equ c 1, Fel d 4, Mus m 1) and albumins (Bos d 6, Can f 3, Equ c 3, Fel d 2) might be very useful to evaluate the possibility of cross-reactions between the allergens of different animals. In fact, allergic sensitization without animal exposure is a relevant risk for patients, because they are not aware about the possibility that even severe respiratory symptoms may develop after an occasional animal contact. This aspect should be taken into account by susceptible individuals before acquiring new pets, after removal of common pets or beginning a contact for working / leisure activity with a common as well as uncommon animal.

The role of albumin receptors in regulation of albumin homeostasis: Implications for drug delivery.

Albumin is the most abundant protein in blood and acts as a molecular taxi for a plethora of small insoluble substances such as nutrients, hormones, metals and toxins. In addition, it binds a range of medical drugs. It has an unusually long serum half-life of almost 3weeks, and although the structure and function of albumin has been studied for decades, a biological explanation for the long half-life has been lacking. Now, recent research has unravelled that albumin-binding cellular receptors play key roles in the homeostatic regulation of albumin. Here, we review our current understanding of albumin homeostasis with a particular focus on the impact of the cellular receptors, namely the neonatal Fc receptor (FcRn) and the cubilin-megalin complex, and we discuss their importance on uses of albumin in drug delivery.

Evaluation of Prognostic Nutritional Index in Patients Undergoing Radical Surgery with Nonsmall Cell Lung Cancer.

The prognostic nutritional index (PNI) has been reported to be a prognostic indicator in some malignant tumors. However, its prognostic value in nonsmall cell lung cancer (NSCLC) has not been fully investigated. A retrospective review of 1416 patients with NSCLC who underwent radical surgery between January 2006 and December 2011 was conducted. To obtain optimal cutoff levels of PNI, running log-rank statistics was applied. Survival was calculated by the Kaplan-Meier method. The prognostic significance of PNI, together with various clinicopathological factors, was evaluated by multivariate analysis. The optimal cutoff point for PNI was 52. The 1-, 3-, and 5-yr survival rates in patients with PNI of less than 52 were 80.0%, 61.3%, and 50.4%, respectively, and were significantly more unfavorable than those in patients with PNI 52 or higher (84.7%, 71.5%, and 60.3%, respectively, P < 0.001). Multivariate analysis suggested that gender (P = 0.026), age (P < 0.001), PNI (P = 0.005), differentiation (P = 0.024), pathology T category (P = 0.003), and pathology N category (P < 0.001) were revealed to be independent prognostic factors. Our results indicate that PNI is an independent predictor of survival for patients undergoing radical surgery with NSCLC.

Hsa-miR-331-3p inhibits VHL expression by directly targeting its mRNA 3'-UTR in HCC cell lines.

Dysregulation of miRNA is widely involved in human cancers, including hepatocellular carcinoma (HCC). Array data for miRNAs indicated that miR-331-3p might be one of the disorderly expressed miRNAs in HCC cell lines, but the function of miR-331-3p in HCC remains unclear. In this study, quantitative real time polymerase chain reaction (qRT-PCR) results indicated that miR-331-3p was up-regulated in HepG2.2.15 cells, Ad-HBV-HepG2 cells and pCH9/3091 transfected SMMC7721 cells compared with their control group, respectively. miRNA target prediction software was used, and VHL was found to be one of the target genes of miR-331-3p. qRT-PCR and western blot analysis indicated VHL expression was decreased when miR-331-3p was over-expressed and increased when miR-331-3p was inhibited in SMMC7721 cells. The luciferase reporter activity was inhibited in SMMC7721 cells when co-transfected with miR-331-3p expression vector and VHL 3'-UTR wild type vector and increased in HepG2.2.15 transfected with miR-331-3p inhibitor compared to its control group respectively. When co-transfected with miR-331-3p expression vector and VHL 3'-UTR mutated type vector in SMMC7721 cells the luciferase reporter activity was recovered. All of these results show that HBV up-regulated miR-331-3p expression in HCC cell lines and miR-331-3p could inhibit VHL expression by directly targeting its 3'-UTR. This provided useful information in exploring the mechanism of HCC induced by HBV infection.

Glycated albumin triggers fibrosis and apoptosis via an NADPH oxidase/Nox4-MAPK pathway-dependent mechanism in renal proximal tubular cells.

Glycated albumin (GA), an Amadori product used as a marker of hyperglycemia and the early-stage glycation products compared to AGEs, might further promote kidney lesions in diabetic nephropathy (DN). However, the mechanisms how GA cause proximal tubular cells damage remain poorly understood. In this study, we investigated the effects of GA on fibrosis and apoptosis of renal proximal tubular cells (NRK-52E) in vitro experiments. Our results showed that GA promoted α-SMA, fibronectin (FN) and TGF-ß expressions in NRK-52E cells. GA also increased cell apoptosis and stimulated the expressions of pro-caspase 3/cleaved-caspase 3. GA overloading enhanced the phosphorylation of MAPK pathway. GA-induced α-SMA, FN, TGF-ß and caspase 3 expressions were completely suppressed by the NADPH oxidase inhibitor apocynin (Apo), the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the latent antioxidant Astragaloside IV (AS-IV). Real-time PCR showed that GA increased Nox1, Nox2 and Nox4 mRNA expressions, especially the Nox4 expression. Furthermore, Nox4 siRNA blocked GA-induced tubular damages and the MAPK pathway activation. These results demonstrate that GA increases the permissiveness of proximal tubular cells to fibrosis and apoptosis in vitro by triggering a pathway that involves NADPH oxidase/Nox4-MAPK signaling pathway. This event may represent a key cellular effect in increasing the susceptibility of tubular cells to fibrosis and apoptosis when the tubules cope with a high GA load. This effect is instrumental to renal damage and disease progression in patients with DN.

Does insulin impact cold-induced fluid- and protein-extravasation?

BACKGROUND: Insulin has been shown to stabilize the endothelial barrier via inactivation of the endothelial contractile machinery and enhancement of cell-cell adhesions. Here we explored if insulin by its endothelial-stabilizing and anti-inflammatory properties could influence the increase of fluid- and protein-extravasation during hypothermia. METHODS: Two groups of animals (n=10, each) were cooled to 28°C, with insulin-infusion (I-group) or without (C-group), in a randomly controlled study. Fluid balance, hemodynamics, plasma volume (PV), colloid osmotic pressures in plasma (COPp) and interstitial fluid (COPi), hematocrit (Hct), cytokine profiles, serum-albumin- and protein-concentrations were measured and fluid extravasation rate (FER) and albumin-and protein-masses calculated. RESULTS: During 240 min of hypothermia the albumin- and protein-masses together with COPp decreased significantly in both groups. COPi remained essentially unchanged. Plasma volume decreased significantly in the C-group, whereas only a decreasing trend was present in the I-group. Hemoconcentration was significant in both study groups reflected by the Hct-values. A slight increasing trend of FER was seen in both groups from 0.10 (0.04) ml/kg/min and 0.09 (0.05) mg/kg/min, C-group and I-group, respectively, to 0.14 (0.05) mg/kg/min and 0.12 (0.03) mg/kg/min, during the hypothermic period. Between-group differences were absent for all listed parameters including FER. CONCLUSION: Insulin administration does not impact fluid and protein extravasation significantly in animals undergoing cooling and prolonged hypothermia.

[Current role of albumin in critical care]. / Papel actual de la albúmina en cuidados críticos.

The use of colloids in fluid therapy has been, and still continues to be a controversial topic, particularly when referring to the critical patient. The choice of the fluid that needs to be administered depends on several factors, many of which are theoretical, and continue being an object of debate. The interest in the clinical use of the albumin has emerged again, immediately after recent publications in the search of the most suitable colloid. It is the most abundant protein in the plasma, being responsible for 80% of the oncotic pressure. It regulates the balance between the intra- and extra-vascular volumes. Recent multicenter studies question the supposed lack of safety that was previously assigned to it. Furthermore, in vitro studies demonstrate other important actions besides oncotic, for example neutralization of free radicals, and exogenous (drugs) and endogenous substances (bile pigments, cholesterol). Being aware of these secondary properties of albumin, and evaluating the pathophysiology of the critical patient (in particular, sepsis), to maintain plasma albumin levels within the normal range, could be of great importance. Based on the most recent publications, the aim of this review is to briefly analyze the pathophysiology of albumin, as well as to discuss its possible indications in the critical patient.

Deciphering metal-induced oxidative damages on glycated albumin structure and function.

BACKGROUND: Metal ions such as copper or zinc are involved in the development of neurodegenerative pathologies and metabolic diseases such as diabetes mellitus. Albumin structure and functions are impaired following metal- and glucose-mediated oxidative alterations. The aim of this study was to elucidate effects of Cu(II) and Zn(II) ions on glucose-induced modifications in albumin by focusing on glycation, aggregation, oxidation and functional aspects. METHODS: Aggregation and conformational changes in albumin were monitored by spectroscopy, fluorescence and microscopy techniques. Biochemical assays such as carbonyl, thiol groups, albumin-bound Cu, fructosamine and amine group measurements were used. Cellular assays were used to gain functional information concerning antioxidant activity of oxidized albumins. RESULTS: Both metals promoted inhibition of albumin glycation associated with an enhanced aggregation and oxidation process. Metal ions gave rise to the formation of ß-amyloid type aggregates in albumin exhibiting impaired antioxidant properties and toxic activity to murine microglia cells (BV2). The differential efficiency of both metal ions to inhibit albumin glycation, to promote aggregation and to affect cellular physiology is compared. CONCLUSIONS AND GENERAL SIGNIFICANCE: Considering the key role of oxidized protein in pathology complications, glycation-mediated and metal ion-induced impairment of albumin properties might be important parameters to be followed and fought.