Glyoxal Levels Research Articles

Identification of a potent NAFLD drug candidate for controlling T2DM-mediated inflammation and secondary damage in vitro and in vivo.

Accumulation of glucose/sugar results in the formation of reactive di-carbonyl compounds such as MGO and GO that interact with several amino acids and proteins to form toxic advanced glycation end products (AGEs). Induction of AGEs breakdown can control symptoms and severity in T2DM and other related complications like NAFLD where AGEs are the key players. Therefore, an AGE cross-link breaker has been suggested for preventing the onset/progression of NAFLD. In this study, we reported novel synthetic naphthalene-2-acyl thiazolium derivatives (KHAGs). Among synthesized KHAG derivatives, we observed that a novel KHAG-04, a 1,4-dimethoxynaphthalen-2-acyl thiazolium salt which is an analog of alagebrium, dramatically cleaves MGO/GO-AGE cross-links, and it also inhibited inflammation by lowering the level of nitric oxide production and IL-1β and TNF-α secretion in LPS and/or MGO-AGE–activated macrophage. Moreover, it also reduced FFA and MGO-AGE–induced lipogenesis in Hep-G2 cells. In mice, KHAG-04 significantly reduced the level of glyoxal in the liver, which was induced by DMC. Furthermore, KHAG-04 treatment significantly reduced blood glucose levels, lipid accumulation, and inflammation in the NAFLD/T2DM animal model. Novel KHAG-04–mediated induction of AGEs breakdown could be the possible reason for its anti-inflammatory, antihyperglycemic, and anti-lipidemic effects in cells and NAFLD in the T2DM animal model, respectively. Further research might explore the pharmacological efficacy and usefulness and consider the ability of this compound in the treatment strategy against various models of NAFLD in T2DM where MGO/GO-AGEs play a key role in the pathogenesis.

The Association of Nε-Carboxymethyllysine With Polyunsaturated and Saturated Fatty Acids in Healthy Individuals.

Red blood cell (RBC) fatty acid status is used as a biomarker of dietary intake of fats; however, there is still a paucity of evidence regarding individual fatty acids and modulation of endogenous advanced glycation end product (AGE) levels. Due to membrane polyunsaturated fatty acid (PUFA) being a well-known target for peroxidation, we hypothesized that cellular PUFAs are positively associated with circulatory Nε-carboxymethyllysine (CML) that is also influenced by glyoxal levels in healthy cohorts. To test this, we investigated the association between RBC fatty acids and circulatory AGE biomarkers in healthy individuals. The results showed a negative association between saturated fatty acids (SFA) and CML, and stepwise multivariate regression analysis indicated that stearic acid was negatively associated with CML levels (β = -0.200, p = .008) after adjusting for age, body mass index (BMI), and gender. In addition, stearic acid:palmitic acid ratio was also negatively correlated with plasma concentrations of CML (rp = -.191, p = .012) and glucose (rp = -.288, p = .0001). PUFAs showed a positive association with CML levels, particularly docosapentaenoic acid, γ-linolenic acid, arachidonic acid, and docosadienoic acid. However, these associations were not evident after the multiple regression analysis adjusted for age, BMI, and gender. A strong negative correlation (rp = -.98, p < .0001) between total PUFA and total SFA was observed. Furthermore, the SFA:PUFA ratio was inversely correlated with CML (rp = -.227, p < .003). Overall, this study indicates that different fats and their combinations may influence the formation of AGEs and that carefully controlled interventions are required to further test this hypothesis.

Low glucose and high pyruvate reduce the production of 2-oxoaldehydes, improving mitochondrial efficiency, redox regulation, and stallion sperm function†.

Energy metabolism in spermatozoa is complex and involves the metabolism of carbohydrate fatty acids and amino acids. The ATP produced in the electron transport chain in the mitochondria appears to be crucial for both sperm motility and maintaining viability, whereas glycolytic enzymes in the flagella may contribute to ATP production to sustain motility and velocity. Stallion spermatozoa seemingly use diverse metabolic strategies, and in this regard, a study of the metabolic proteome showed that Gene Ontology terms and Reactome pathways related to pyruvate metabolism and the Krebs cycle were predominant. Following this, the hypothesis that low glucose concentrations can provide sufficient support for motility and velocity, and thus glucose concentration can be significantly reduced in the medium, was tested. Aliquots of stallion semen in four different media were stored for 48h at 18°C; a commercial extender containing 67mM glucose was used as a control. Stallion spermatozoa stored in media with low glucose (1mM) and high pyruvate (10mM) (LG-HP) sustained better motility and velocities than those stored in the commercial extender formulated with very high glucose (61.7 ± 1.2% in INRA 96 vs 76.2 ± 1.0% in LG-HP media after 48h of incubation at 18°C; P < 0.0001). Moreover, mitochondrial activity was superior in LG-HP extenders (24.1 ± 1.8% in INRA 96 vs 51.1 ± 0.7% in LG-HP of spermatozoa with active mitochondria after 48h of storage at 18°C; P < 0.0001). Low glucose concentrations may permit more efficient sperm metabolism and redox regulation when substrates for an efficient tricarboxylic acid cycle are provided. The improvement seen using low glucose extenders is due to reductions in the levels of glyoxal and methylglyoxal, 2-oxoaldehydes formed during glycolysis; these compounds are potent electrophiles able to react with proteins, lipids, and DNA, causing sperm damage.

Long-term incubation of myoglobin with glyoxal induces amyloid like aggregation of the heme protein: Implications of advanced glycation end products in protein conformational disorders

Protein glycation is a post-translational modification of proteins which is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. The reactive α-dicarbonyl compound, glyoxal, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the current study, the effect of glyoxal on the monomeric protein myoglobin has been investigated following incubation for a period of 30 days. Long-term incubation with glyoxal induced alteration of secondary structure of the heme protein from α-helix to β-sheet resulting in aggregation of the protein. The aggregates were found to exhibit amyloidal features with amorphous morphology as evident from subsequent biophysical spectroscopic and microscopic studies. Finally, mass spectrometric studies revealed glyoxal-induced modification of Lys-96, Lys-118, Lys-145, Arg-31 and Arg-139 residues of myoglobin to AGE adducts. The AGEs detected and identified were carboxymethyllysine (Lys-96), pyrrolidone-carboxymethyllysine (Lys-96, Lys-118 and Lys-145), arginine-derived hydroimidazolone (Arg-31) and the cross-linking adduct pentosidine (Lys-145 and Arg-139). Thus glyoxal-derived AGE adducts appear to induce structural constrain and subsequent aggregation of the heme protein. Considering the increased level of glyoxal in diabetes and the significance of AGE-mediated protein modification, the present study appears clinically relevant in understanding AGE-induced protein modification and subsequent conformational disorders.

Effect of Glyoxal Modification on a Critical Arginine Residue (Arg-31α) of Hemoglobin: Physiological Implications of Advanced Glycated end Product an in vitro Study.

Non-enzymatic protein glycation is involved in structure and stability changes that impair protein functionality, resulting in several human diseases, such as diabetes and amyloidotic neuropathies (Alzheimer's disease, Parkinson's disease and Andrade's syndrome). Glyoxal, an endogenous reactive oxoaldehyde, increases in diabetes and reacts with several proteins to form advanced glycation end products through Maillard-like reaction. Human hemoglobin, the most abundant protein in blood cells is subjected to nonenzymatic modification by reactive oxoaldehydes in diabetic condition. In the present study, the effect of a low concentration of glyoxal (5 μM) on hemoglobin (10 μM) has been investigated following a period of 30 days incubation in vitro. Different techniques, mostly biophysical and spectroscopic (e.g. circular dichroism, differential scanning calorimetric study, dynamic light scattering, mass spectrometry, etc.) were used to study glyoxal-induced changes of hemoglobin. Glyoxal-treated hemoglobin exhibits decreased absorbance around 280 nm, decreased fluorescence and reduced surface hydrophobicity compared to normal hemoglobin. Glyoxal treatment enhances the stability of hemoglobin and lowers its susceptibility to thermal aggregation compared to control hemoglobin as seen by different studies. Finally, peptide mass fingerprinting study showed glyoxal to modify an arginine residue of α-chain of hemoglobin (Arg-31α) to hydroimidazolone. Increased level of glyoxal in diabetes mellitus as well as its high reactivity may cause modifications of the heme protein. Thus, considering the significance of glyoxal-induced protein modification under physiological conditions, the observation appears clinically relevant in terms of understanding hydroimidazolone-mediated protein modification under in vivo conditions.

Free Fructose Intake Decreases Soluble RAGE Receptor (sRAGE) and Glyoxal and Methylglyoxal Urinary Excretion on Healthy Volunteers

Abstract Objectives Free fructose but not total fructose intake could contribute to the formation of advanced glycation end products (AGEs) and Maillard reaction products in the intestinal lumen. Therefore, the aim of this study was to compare serum levels of fructosamine, soluble receptor for AGEs (sRAGE), and urinary levels of glyoxal and methylglyoxal after free fructose and total fructose intake. Methods This is a randomized crossover study, approved by the Institutional Committee of Bioethics in Research of the University of Guanajuato (CIBIUG). Twelve clinically healthy subjects, 20–30 years old, were recruited. During the first visit, participants were randomly assigned to one of two treatments, an oral load of fructose (40 g) or total fructose (40 g fructose and 40 g glucose), in addition to their assigned treatment subjects received 25 g of hydrolyzed protein (Nature Best Isopure®) After a washing period (one week), participants were crossed over to receive the other treatment. Blood and urine samples were collected at baseline and after three hours of the oral load of each treatment. Glucose, creatinine, and lipids serum levels were measured with commercial kits. Insulin, fructosamine, and sRAGE serum levels were determined with ELISA commercial kits. Glyoxal and methylglyoxal urine levels were quantified by HPLC. Data analysis was completed using STATISTICA 10 and IBM SPSS Statistics 24.0 software. The results were considered significant with a value of P &amp;lt; 0.05. Results After free Fructose intake, participants had a significant decrease in sRAGE (1327 pg/L vs 1282 pg/L, P = 0.028), and in urine levels of glyoxal (0.63 ng/mg vs 0.24 ng/mg P = 0.028) and methylglyoxal (0.42 ng/mg vs 0.13 ng/mg P = 0.002). After Fructose and glucose intake, participants only had a significant decreased in serum sRAGE (1256 pg/L vs 1199 pg/L, P = 0.015). Fructosamine did not showed a difference after either intervention. Conclusions The consumption of free fructose decreased serum sRAGE levels, as well as urinary excretion of glyoxal and methylglyoxal. These results may suggest a possible in vivo formation of AGEs by consuming free fructose. Nevertheless, more studies are necessary to assess the formation of methylglyoxal derived AGEs. Funding Sources This project was supported by the University of Guanajuato through the Research and Postgraduate Support Department (DAIP).

Comprehensive Chemical Characterization of the Aerosol Emissions of a Vaping Product Based on a New Technology.

Around 10 million people in the United States and 3 million people in the United Kingdom are estimated to use vaping category products. There are some estimates that there will be 75–80 million vapers worldwide by 2020. Most of these products are based on coil-and-wick technology. Because the heating and aerosol formation are separate processes, the system can lead to dry-wicking and elevated emission of carbonyls if designed and/or manufactured poorly. Low-nicotine and low-power coil-and-wick devices have also been linked to increased exposure to formaldehyde due to compensatory behavior by users. We characterized the emissions of a vaping product which uses a fabric-free stainless-steel mesh distiller plate technology that heats and aerosolizes the e-liquid in a single process. The plate has a microporous structure for capillary-induced liquid transformation (wicking) and aerosolization that is optimized to avoid fluid starvation and overheating and improved control. Compared with emissions previously reported for a coil-and-wick nicotine vaping product (e-cigarette), most classes of harmful and potentially harmful constituents (HPHCs) from this vaping product were below the level of detection or quantification. For those that were quantifiable, this vaping product generally had lower levels of emissions than the e-cigarette, including carbonyls. Formaldehyde and methyl glyoxal levels did not differ significantly between vaping products. In this system, the single mode of liquid transfer and vapor formation permits high aerosol mass delivery but further reduces emissions of HPHCs that may be present in conventional e-cigarette aerosol, by lessening the risk of thermal breakdown of the aerosol-generating solvent mixture.

Metabolic signature of methylone in primary mouse hepatocytes, at subtoxic concentrations.

Methylone (3,4-methylenedioxymethcathinone) is one of the most popular new psychoactive drugs worldwide. Although advertised as a safe drug, its use has been associated to several cases of liver damage. In this work, a metabolomics approach based on gas chromatography-mass spectrometry (GC-MS) combined with chemometric analyses was used to characterize the disturbances occurring in the intra- and extracellular metabolome of primary mouse hepatocytes exposed to two subtoxic concentrations (LC01 and LC10) of methylone to better understand the early hepatotoxic events. Results showed a characteristic metabolic fingerprint for methylone, where aspartate, cysteine, 2-methyl-1-pentanol, 4-methylheptane, dodecane, 2,4-dimethyl-1-heptene, 1,3-di-tert-butylbenzene, acetophenone, formaldehyde and glyoxal levels were significantly changed at both concentrations tested. Furthermore, subtoxic concentrations of methylone caused profound changes in several biochemical pathways, suggesting adaptations in energy production processes (TCA cycle, amino acids metabolism and pyruvate metabolism), cellular antioxidant defenses (glutamate, cysteine and glutathione metabolism) and hepatic enzymes (associated to hydrocarbons, alcohols, aldehydes and ketones metabolism). This metabolic response to the initial methylone challenge most probably reflects the activation of protective mechanisms to restore cellular homeostasis. Overall, this study highlights the potential of untargeted metabolomic analysis to reveal the hepatic metabolic signature of methylone at subtoxic concentrations, and also provides clues to clarify the early mechanisms underlying the toxicity triggered by this new psychoactive substance, opening a new perspective for the study of toxicity mechanisms of new xenobiotics.

Formation of α-Dicarbonyls from Dairy Related Carbohydrates with and without Nα-Acetyl-l-Lysine during Incubation at 40 and 50 °C.

α-Dicarbonyls are reactive intermediates formed during Maillard reactions and carbohydrate degradation. The formation of seven α-dicarbonyls was characterized in solutions containing dairy related carbohydrates (galactose, glucose, lactose, and galacto-oligosaccharides (GOS)) during incubations at 40 and 50 °C with and without Nα-acetyl-l-lysine at pH 6.8 for up to 2 months. The concentrations of α-dicarbonyls in samples of monosaccharides with Nα-acetyl-l-lysine were found to be 3-deoxyglucosone (3-DG) > 3-deoxygalactosone (3-DGal) > glyoxal > glucosone, galactosone > methylglyoxal > diacetyl. The presence of Nα-acetyl-l-lysine resulted in up to 100-fold higher concentrations of C6 α-dicarbonyls but lesser formation of glyoxal in the monosaccharide-containing models compared to what was observed in the absence of Nα-acetyl-l-lysine. Galactose incubated with Nα-acetyl-l-lysine generated the highest concentrations of 3-DGal (up to 130 μM), glyoxal (up to 100 μM), and methylglyoxal (up to 9 μM) compared to the other carbohydrates during incubation. Surprisingly, 3-DG (1500 μM) and 3-DGal (80 μM) were formed at levels of 2 orders of magnitude higher in solutions of GOS in the absence of Nα-acetyl-l-lysine as compared to the other carbohydrates at 40 °C, while GOS generated the lowest levels of glyoxal. GOS are widely used as an ingredient in various types of foods products, and it is therefore of importance to consider the risk of generating high levels of the reactive C6 α-dicarbonyl, 3-DG, in these types of products. This study contributes to the understanding of major α-dicarbonyl formation as affected by the presence of primary amines in GOS-, lactose-, and galactose-containing solutions under moderate heating in liquid foods.

Elevated levels of glyoxal and methylglyoxal at a remote mountain site in southern China: Prompt in-situ formation combined with strong regional transport

The dicarbonyls glyoxal (Gly) and methylglyoxal (Mgly) are key tracers for the oxidation of volatile organic compounds (VOCs) in the atmosphere, but their atmospheric chemistry in remote forest environments is not well understood. A study was carried out during Jul. 31–Nov. 5 of 2016 at the summit of Mt. Tianjing (1690 m.a.s.l.), a remote mountaintop site in southern China, to measure the levels of Gly and Mgly and explore their sources and fate. During the study period, the average mixing ratios of Gly and Mgly were 509 ± 31 pptv and 340 ± 32 pptv, respectively, with the Gly/Mgly ratios averaging 1.8 ± 0.2. Both the dicarbonyl concentrations and the Gly/Mgly ratios were significantly higher than those observed in other background sites. Production yield calculations and meteorological data analysis indicate that high levels of Gly and Mgly observed at the study site were largely a combined result of rapid in-situ formation and regional transport by prevailing winds. On average, in-situ formation from precursors is estimated to account for 67% of the observed Mgly and about 9% of the observed Gly. There were significant changes in Gly and Mgly mixing ratios among different time periods when air masses from different source regions dominated, indicating contribution of regional transport to the observed dicarbonyl mixing ratios at the study site. Biogenic emissions in eastern China and anthropogenic emissions in the Pearl River Delta region were the two main sources responsible for the dicarbonyls observed at the site during most of the sampling period, but large-scale biomass burning in central China was also important in the late autumn, as supported by a backward trajectory analysis of fire spot data and the identification of biomass burning tracers. This study provides insights into the background atmospheric chemistry and the impact of biogenic and anthropogenic sources on the dicarbonyls speciation.

Impact of resveratrol, epicatechin and rosmarinic acid on fluorescent AGEs and cytotoxicity of cookies

In this study, cookies were incorporated with three polyphenols (rosmarinic acid, resveratrol, and epicatechin) at two concentrations (0.02% and 0.2%), and baked under three temperatures (150, 170, and 190 °C) to observe their interaction. They didn’t significantly change the cookie texture, but influence the color and pH. Temperature was a significant determinant to affect polyphenols’ stability and accordingly influenced cookies’ antioxidant capacity. 73.4%, 26.7% and 9.9% of rosmarinic acid, resveratrol, and epicatechin remained after baking at 190 °C for 10 min. Two addition levels of polyphenols decreased fluorescent advanced glycation endproducts (AGEs) by 18.58% to 40.29% and 28.60% to 62.05% respectively, while only resveratrol and epiatechin could reduce the level of glyoxal and methylglyoxal in cookies. In addition, we discovered that thermal processing could enhance the cytotoxicity of rosmarinic acid against cancer cells. Thus polyphenols were suggested as beneficial additives for enhancing antioxidant intake and lowering total fluorescent AGEs.

Glyoxal-induced modification enhances stability of hemoglobin and lowers iron-mediated oxidation reactions of the heme protein: An in vitro study

Glyoxal, a reactive α-oxoaldehyde, increases in diabetic condition. It reacts with different proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. Considering the significance of AGE-mediated protein modification by glyoxal, here we have investigated the in vitro effect of the reactive α-oxoaldehyde (10, 20μM) on the heme protein hemoglobin (HbA0) (100μM) after incubation for one week at 25°C. In comparison with HbA0, glyoxal-treated HbA0 exhibited decreased absorbance around 280nm, reduced intrinsic fluorescence and lower surface hydrophobicity. Glyoxal treatment was found to increase the stability of HbA0 without significant perturbation of the secondary structure of the heme protein. In addition, H2O2-mediated iron release and subsequent iron-mediated oxidative (Fenton) reactions were found to be lower in presence of glyoxal-treated HbA0 compared to HbA0. Mass spectrometric studies revealed modification of arginine residues of HbA0 (Arg-31α, Arg-40β) to hydroimidazolone adducts. AGE-induced modifications thus appear to be associated with the observed changes of the heme protein. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, glyoxal-derived AGE adducts might thus be associated with modifications of the protein including physiological significance.

Dispersive liquid-liquid microextraction for a rapid determination of glyoxal in alcoholic beverages

Carbonyl compounds, like glyoxal, methylglyoxal, diacetyl or pentane-2,3-dione, among others, have been widely studied. Besides its endogenous origin, they are originated from foodstuffs and are related to sensorial characteristics in products such as wine and beer. Generally, for their determination, the analytes must be derivatised to adapt them for the detection system and this step takes long time. The main aim of this research was to develop a simultaneous derivatization and extraction method which takes place in only few minutes. 3,4-diaminopyridine, as derivatizing reagent, generate a fluorescent product. This reaction is selective for glyoxal. For this new dispersive liquid-liquid microextraction (DLLME) procedure combined with chromatographic determination of glyoxal, various parameters affecting the extraction were optimized and finally, a mixture of butan-1-ol as dispersant solvent and dichloromethane as extractant solvent were selected. Its chromatographic peak appears at 2.6min. Four Spanish wines and five Spanish beers have been analysed and the results showed that the levels of glyoxal are comprised between 2.8–9.5mgL−1. The proposed DLLME method drastically reduces the reaction time from 2 or 3–20min improving the methods found in the literature. The glyoxal concentration found in the wines and beers analysed do not suppose any health risk.

Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study

Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant.

The protective effect of metformin on hypertriglyceridemia-induced dicarbonyl stress in serum and tissues

s / Atherosclerosis 241 (2015) e32ee71 e58 EAS-0142. THE PROTECTIVE EFFECT OF METFORMIN ON HYPERTRIGLYCERIDEMIAINDUCED DICARBONYL STRESS IN SERUM AND TISSUES V. Skop, H. Malinska, J. Trnovska, L. Kazdova. Center for Experimental Medicine, Institute for Clinical and Experimental Medicine Prague Czech Republic, Prague 4, Czech Republic Biogenesis of reactive dicarbonyls leads to the production of advanced glycation end products, increases oxidative stress, and play a key role in the development of diabetic vascular complications. Metformin is the most widely prescribed glucose-lowering agent; however, its effect on dicarbonyls metabolism in tissues is not clarified. In our study we analyzed levels of individual reactive dicarbonyls e methylglyoxal (MG), glyoxal (GL) and 3-deoxyglucosone (3-DG) in relation to lipid disorders and after metformin administration (300 mg/kg b.wt.) in non-obese hereditary hypertriglyceridemic (HHTg) rats. The concentration of dicarbonyls were determined by derivatisation with 1,2-diamino-4,5-dimethoxy-benzene and HPLC-method with fluorescence detection. Compared with control Wistar rats, HHTg rats exhibited markedly increased serum level of GL (+89%) and MG (+179%), increased levels of GL (+189%), MG (+73%) and 3-DG (+114%) in myocardium and increased level of GL (+59%) and MG (+57%) in kidney cortex. Metformin treatment significantly reduced level of reactive dicarbonyls in the myocardium (Gl: -31%; MG: -15%; 3-DG: -49%) and reduced level of MG (-49%) in serum. However, dicarbonyls concentrations in the kidney cortex were not affected by metformin. Changes in dicarbonyls concentrations were accompanied by changes in glutathione metabolism. Metformin prevents negative effect of hypertriglyceridemia on GSH/GSSG ratio and total glutathione content in myocardium, but neither hypertriglyceridemia nor metformin affects glutathione metabolism in kidney cortex. Results indicate that hypertriglyceridemia is associated with increased dicarbonyl stress in serum and tissues. Beneficial effect of metformin therapy on reactive dicarbonyls in heart could contribute to its cardioprotective effects. Supported by the grant GACR P303/13-04420S EAS-0202. MILK INTAKE IS NOT CAUSALLY ASSOCIATED WITH RISK OF ISCHEMIC HEART DISEASE OR MYOCARDIAL INFARCTION e A MENDELIAN RANDOMIZATION STUDY IN 98,529 DANISH INDIVIDUALS H.K.M. Bergholdt , B.G. Nordestgaard , A. Varbo , C. Ellervik . Dept. of Clinical Biochemistry, Naestved Hospital, Naestved, Denmark; Dept. of Clinical Biochemistry, Copenhagen University Hospital, Herlev, Denmark; 3 Faculty of Health and Medical Sciences, University of Copenhagen,

Glyoxal observations in the global marine boundary layer

AbstractGlyoxal is an important intermediate species formed by the oxidation of common biogenic and anthropogenic volatile organic compounds such as isoprene, toluene, and acetylene. Although glyoxal has been shown to play an important role in urban and forested environments, its role in the open ocean environment is still not well understood, with only a few observations showing evidence for its presence in the open ocean marine boundary layer (MBL). In this study, we report observations of glyoxal from 10 field campaigns in different parts of the world's oceans. These observations together represent the largest database of glyoxal in the MBL. The measurements are made with similar instruments that have been used in the past, although the open ocean values reported here, average of about 25 parts per trillion by volume (pptv) with an upper limit of 40 pptv, are much lower than previously reported observations that were consistently higher than 40 pptv and had an upper limit of 140 pptv, highlighting the uncertainties in the differential optical absorption spectroscopy method for the retrieval of glyoxal. Despite retrieval uncertainties, the results reported in this work support previous suggestions that the currently known sources of glyoxal are insufficient to explain the average MBL concentrations. This suggests that there is an additional missing source, more than a magnitude larger than currently known sources, which is necessary to account for the observed atmospheric levels of glyoxal. Therefore, it could play a more important role in the MBL than previously considered.

Induction of amyloidogenicity in wild type HEWL by a dialdehyde: Analysis involving multi dimensional approach

Physiological conditions corresponding to oxidative stress deplete the level of enzyme glyoxalase, facilitating a hike in the serum concentration of glyoxal. Simulating an elevated in vivo level of glyoxal, we tested (50%, v/v) concentration of glyoxal to interact with HEWL. Initially, docking study revealed that glyoxal binds in the hydrophobic core of the enzyme. The interaction between the dialdehyde (glyoxal) and the enzyme (HEWL) followed a three step transition involving pre-molten and molten globule states formed on days 7 and 15 of incubation respectively, which were characterised by an increase in the ANS fluorescence intensity compared to the native state. These molten globule states upon further incubation on day 20 resulted in the formation of aggregates which were characterised by an increase in ThT fluorescence intensity, red shift in Congo red absorbance, negative ellipticity peak at 217nm in the far-UV CD and the loss of signals at 284, 290 and 294nm in the near-UV CD spectra. Finally, TEM confirmed the authenticity of lysozyme fibril formation by displaying rod like fibrillar structure.

Response surface methodology as optimization strategy for reduction of reactive carbonyl species in foods by means of phenolic chemistry

Response surface methodology (RSM) was utilized to investigate the dose-response relationships of a phenolic mixture (catechin, genistein and daidzein) as a pre-thermal processing technique to reduce reactive carbonyl species (RCSs; glyoxal, methylglyoxal and 3-deoxyglucosone) in ultra-high temperature (UHT) bovine milk. A modified derivatization technique for RCSs was developed to overcome quantitative error caused by interference from the phenolic compounds. For the statistical analysis, a Box-Behnken 3-factor (catechin, genistein and daidzein) 3-level (0.17, 0.645 and 1.12 mM) design was employed. In general, all phenolic mixtures were able to reduce RCSs in UHT milk; some compositions reported RCSs levels at or below levels reported in pasteurized milk. Predictive models with no significant lack of fit (p > 0.05), high R(2)-values (0.886-0.979) and good predictive power were developed. ANOVA analysis of the glyoxal levels indicated that only linear effects of each phenolic compound had a significant effect (p < 0.05) meaning that no significant interactions between the different phenolic compounds influenced glyoxal levels. Linear, cross product and quadratic effects of factors were reported (p < 0.05) for methylglyoxal, indicating more complicated interactions between the phenolic compounds. Both linear and quadratic effects were also reported (p < 0.05) for 3-deoxyglucosone. Overall, based on canonical analysis, catechin seemed to be the most influential factor for the reduction of RCSs in UHT milk. In summary, RSM provided a basis to understand phenolic structure-reactivity and to optimize the composition of a tertiary mixture of phenolic compounds for reduction of RCSs in UHT milk.

Effect of Cd(ii) and Se(iv) exposure on cellular distribution of both elements and concentration levels of glyoxal and methylglyoxal in Lepidium sativum

In this work, the effect of cadmium (0-5.0 mg L(-1) as cadmium chloride, Cd(II)) and selenium (0-2.0 mg L(-1) as sodium selenite, Se(IV)) was studied in Lepidium sativum with specific focus on glyoxal (GO) and methylglyoxal (MGO) and on the cellular distribution of both elements under different exposure conditions. The concentrations of two reactive α-ketoaldehydes present as natural metabolites and as by-products of lipid peroxidation, were increased in plants treated with Cd(II), providng complementary experimental evidence on element phytotoxicity in garden cress, in terms of oxidative damage. Even though for higher than 1.0 mg L(-1) Se in medium similar adverse effect was found, under simultaneous exposure to both elements the changes in GO and MGO concentrations were clearly attenuated as compared to a single stressor treatment. This effect was accompanied by lower uptake of the two elements, significant decrease of their relative distribution in the fraction containing polar compounds and their increase in fraction corresponding to insoluble cell fragments/components, suggesting that the direct in vivo interaction between two element forms might be involved in the favorable effects of simultaneous treatment with Cd(II) + Se(IV). The fluorescence spectra obtained for biomass extracts corresponding to different exposure conditions suggested possible in vivo formation of CdSe quantum dots; however further studies are needed for ultimate identification and characterization of such nanoparticulate species.

DOAS measurements of formaldehyde and glyoxal above a south-east Asian tropical rainforest

Abstract. Tropical rainforests act as a huge contributor to the global emissions of biogenic volatile organic compounds (BVOCs). Measurements of their oxidation products, such as formaldehyde (HCHO) and glyoxal (CHOCHO), provide useful indicators of fast photochemistry occurring in the lower troposphere. However, measurements of these species in tropical forest locations are extremely limited. To redress this, HCHO and CHOCHO were measured using the long-path (LP) and multi-axis (MAX) differential optical absorption spectroscopy (DOAS) techniques above the rainforest canopy in Borneo during two campaigns in spring and summer 2008, as part of the Oxidant and Particle Photochemical Processes above a south-east Asian tropical rainforest (OP3) project. The results were compared with concurrent measurements of hydroxyl radical (OH), isoprene (C5H8) (which was the dominant organic species emitted in this forest environment), and various meteorological parameters. Formaldehyde was observed at a maximum concentration of 4.5 ppb and glyoxal at a maximum of 1.6 ppb, significantly higher than previous measurements in rural locations. A 1-D chemistry model was then used to assess the diurnal evolution of formaldehyde and glyoxal throughout the boundary layer. The results, which compare well with the LP-DOAS and MAX-DOAS observations, suggest that the majority of the glyoxal and formaldehyde is confined to the first 500 m of the boundary layer, and that the measured ratio of these species is reproduced using currently accepted product yields for the oxidation of isoprene by OH. An important conclusion is that the measured levels of glyoxal are consistent with the surprisingly high concentrations of OH measured in this environment.