AGEs accumulation is related to muscle degeneration and vascular calcification in peritoneal dialysis patients / O acúmulo de AGEs está relacionado à degeneração muscular e calcificação vascular em pacientes em diálise peritoneal

Abstract Background: Patients with chronic kidney disease (CKD) are affected by dynapenia, sarcopenia, and vascular calcification. Advanced glycation end products (AGEs) may accumulate in peritoneal dialysis (PD) patients and favor sarcopenia via changes in collagen cross-linking, muscle protein breakdown, and the calcification of arterial smooth muscle cells via p38-MAPK activation. The aim of this study is to explore the relationships between AGEs, muscle degeneration, and coronary artery calcification. Methods: This was a clinical observational study in patients with CKD undergoing PD, in which serum and skin AGEs (AGEs-sAF), cumulative glucose load, muscle strength and functional tests, muscle ultrasounds with elastography, coronary artery calcium (CAC) quantification, and muscle density by multislice computed tomography were measured. Results: 27 patients aged 48±16 years, dialysis vintage of 27±17 months, had AGEs-sAF levels of 3.09±0.65 AU (elevated in 13 [87%] patients), grip strength levels of 26.2±9.2 kg (11 [42%] patients with dynapenia), gait speed of 1.04±0.3 m/s (abnormal in 14 [58%] patients) and "timed-up-and-go test" (TUG) of 10.5±2.2s (abnormal in 7 [26%] patients). Correlations between AGEs-sAF levels and femoral rectus elastography (R=-0.74; p=0.02), anterior-tibialis elastography (R= -0.68; p=0.04) and CAC (R=0.64; p=0.04) were detected. Cumulative glucose load correlated with femoral rectal elastography (R=-0.6; p=0.02), and serum glycated hemoglobin concentrations correlated with psoas muscle density (R= -0.58; p=0.04) and CAC correlated with psoas muscle density (R=0.57; p=0.01) and lumbar square muscle density (R=-0.63; p=0.005). Conclusions: The study revealed associations between AGEs accumulation and lower muscle stiffness/density. Associations that linked muscle degeneration parameters with vascular calcification were observed.

Resumo Histórico: Pacientes com doença renal crônica (DRC) são afetados pela dinapenia, sarcopenia e calcificação vascular. Produtos finais da glicação avançada (AGEs) podem se acumular em pacientes em diálise peritoneal (DP) e favorecer a sarcopenia por meio de alterações em ligações cruzadas do colágeno, quebra da proteína muscular e calcificação das células do músculo liso arterial por meio da ativação da p38-MAPK. O objetivo deste estudo é explorar as relações entre AGEs, degeneração muscular e calcificação da artéria coronária. Métodos: Este foi um estudo clínico observacional em pacientes com DRC submetidos à DP, no qual foram medidos os AGEs séricos e teciduais (AGEs-sAF), a carga cumulativa de glicose, a força muscular e testes funcionais, ultrassonografias musculares com elastografia, quantificação do cálcio da artéria coronária (CAC), e a densidade muscular por tomografia computadorizada multislice. Resultados: 27 pacientes com idade entre 48±16 anos, tempo de diálise entre 27±17 meses, tinham níveis de AGEs-sAF de 3,09±0,65 UA (elevado em 13 [87%] pacientes), níveis de força de preensão de 26,2±9,2 kg (11 [42%] pacientes com dinapenia), velocidade de marcha de 1,04±0,3 m/s (anormal em 14 [58%] pacientes) e teste "timed-up-and-go" (TUG) de 10,5±2,2s (anormal em 7 [26%] pacientes). Foram detectadas correlações entre os níveis AGEs-sAF e a elastografia do reto femoral (R=-0,74; p=0,02), a elastografia tibial anterior (R= -0,68; p=0,04) e a CAC (R=0,64; p=0,04). A carga cumulativa de glicose se correlacionou com a elastografia do reto femoral (R=-0,6; p=0,02), as concentrações séricas de hemoglobina glicada se correlacionaram com a densidade muscular do psoas (R= -0,58; p=0,04) e o CAC se correlacionou com a densidade do músculo psoas (R=-0,57; p=0,01) e a densidade do músculo quadrado lombar (R=-0,63; p=0,005). Conclusões: O estudo revelou associações entre o acúmulo de AGEs e menor rigidez/densidade muscular. Foram observadas associações que ligavam parâmetros de degeneração muscular com a calcificação vascular.

Reacción de Maillard: Efectos patogénicos / Maillard reaction. Pathogenic effects

La cocción de los alimentos a altas temperaturas en calor seco, produce ciertas modificaciones organolépticas que los hace especialmente apetecibles y objetos de adicción. Esto es resultado de la reacción de Maillard, o glicación, que se produce por unión no enzimática del grupo carbonilo, de azúcares reductores como glucosa y fructosa, con el grupo amino de proteínas y ácidos nucleicos. Junto a los cambios físicos, cambia la estructura química y la función de estos aductos, denominados también glicotoxinas. Además de la glicación exógena, generada durante la cocción de los alimentos, recientemente ha sido referida la glicación in situ, en la luz intestinal, durante la digestión, cuando determinados alimentos no glicados se combinan en el momento de su ingestión. A esto se agrega la glicación endógena extracelular relacionada con la glucosa sanguínea y la intracelular, con metabolitos de la glucólisis y de la fructosa. Desde la década del 70, con el remplazo en gran medida de la sacarosa por fructosa, significativamente más reactiva que la glucosa, aumentó la presencia de productos de glicación en alimentos procesados y bebidas gaseosas. Están documentados sus efectos patogénicos como contribuyentes al estrés oxidativo y a la inflamación, especialmente en diabetes, insuficiencia renal y enfermedad cardiovascular y están siendo explorados en otras enfermedades crónicas, como procesos neurodegenerativos y envejecimiento temprano. Se describen medidas para preservar la salud, atendiendo medios de cocción y procesamiento de los alimentos y recomendaciones sobre hábitos de vida e ingesta de antioxidantes para acción inhibitoria o antagónica sobre las glicotoxinas.

Certain organoleptic modifications by way of processing and cooking foods at high temperatures in dry heat, make them especially appetizing and objects of addiction. It results from Maillard reaction, or glycation, consisting of the non-enzymatic union between carbonyl groups, mainly from reducing sugars as glucose and fructose, with the amino group of proteins and nucleic acids. In addition to physical changes, also the chemical structure and function of these compounds are changed. Besides exogenous glycation generated during the cooking of foods, recently in situ glycation has been reported in the intestinal lumen during digestion, when certain non-glycated foods are combined with fructose at the time of ingestion. In addition, endogenous glycation, which correlates in the extracellular mainly with blood glucose and in the intracellular with glycolysis metabolites and fructose, is specially significant. Since the 70s, with the frequent sucrose replacement by fructose, much more reactive than glucose, the presence of glycation products in processed foods and soft drinks increased.Pathogenic effects of these compounds, also called glycotoxins, are known to contribute to oxidative stress and inflammation. This increases progression of chronic diseases, well documented in diabetes, renal insuficiency, cardiovascular disease and aging process, and are being explore d in many other chronic diseases as neurodegenerative disorders and early aging. Based on the knowledge achieved so far, measures to preserve health are described by attending ways of cooking and processing foods, besides recommendations for life habits and antioxidants dietary intakes for inhibition or antagonism on glycotoxins.

Advanced glycation end-products (AGEs) accumulation in skin: relations with chronic kidney disease-mineral and bone disorder / Acúmulo dos produtos finais da glicação avançada (AGEs) na pele: relações com o distúrbio mineral e ósseo na doença renal crônica

Abstract Introduction: Chronic kidney disease (CKD) is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD) and bone mineral disorder (CKD-BMD). Uremic toxins, as advanced glycation end products (AGEs), are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF) is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF) and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group) and healthy subjects (Control group, n = 24), performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH), transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

Resumo Introdução: A doença renal crônica (DRC) apresenta elevadas taxas de morbidade e mortalidade, sendo a doença cardiovascular (DCV) e o distúrbio mineral e ósseo da DRC (DMO-DRC) complicações frequentes. As toxinas urêmicas, dentre elas os produtos finais da glicação avançada (AGEs), são fatores de risco cardiovascular não tradicionais e se encontram envolvidas no desenvolvimento do DMO-DRC na DRC. A medida da autofluorescência da pele (sAF) é método não invasivo para quantificação do acúmulo tecidual de AGEs validado em pacientes portadores de DRC. Objetivos: O objetivo deste estudo é avaliar as relações entre os AGEs medidos por sAF (AGEs-AF) e parâmetros de DCV e DMO-DRC em pacientes em hemodiálise (HD). Métodos: 20 pacientes em HD (grupo HD) e 24 indivíduos hígidos (grupo controle) foram submetidos à análise bioquímica sérica, medidas antropométricas e de sAF. O grupo HD realizou medida de hormônio intacto da paratireoide (PTHi), ecocardiograma transtorácico e radiografias de pelve e mãos para pesquisa de calcificação vascular. Resultados: Os níveis de AGEs-sAF foram elevados para a idade nos grupos HD e controle, porém mais elevados no grupo HD. Sessão única de HD de alto-fluxo não afetou os níveis de AGEs-sAF. Os níveis teciduais de AGEs não se correlacionaram com massa ventricular, espessura de septo interventricular ou calcificação vascular no grupo HD. Os níveis de AGEs-sAF se correlacionaram negativamente com os níveis séricos de PTHi. Conclusão: Nosso estudo detectou correlação negativa entre os níveis de AGEs-sAF e os níveis séricos de PTHi, sugerindo que os AGEs estejam envolvidos na fiosiopatologia da doença óssea em pacientes em HD. A natureza desta relação e a aplicação clínica deste método não invasivo de avaliação do acúmulo tecidual de AGEs deve ser confirmada e elucidada por estudos futuros.

Interaction between ascorbic acid and gallic acid in a model of fructose-mediated protein glycation and oxidation

Background: Dietary plant-based foods contain combinations of various bioactive compounds such as phytochemical compounds and vitamins. The combined effect of these vitamins and phytochemicals remains unknown, especially in the prevention of diabetes and its complications. The present study aimed to investigate the combined effect of ascorbic acid and gallic acid on fructose-induced protein glycation and oxidation. Results: Ascorbic acid (15 µg/mL) and gallic acid (0.1 µg/mL) reduced fructose-induced formation of advanced glycation end products (AGEs) in bovine serum albumin (BSA; 10 mg/mL) by 15.06% and 37.83%, respectively. The combination of ascorbic acid and gallic acid demonstrated additive inhibition on the formation of AGEs after 2 weeks of incubation. In addition, synergistic inhibition on the formation of amyloid cross-ß structure and protein carbonyl content in fructose-glycated BSA was observed. At the same concentration, the combination of ascorbic acid and gallic acid produced a significant additive effect on the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. Conclusion: Combining natural compounds such as ascorbic acid and gallic acid seems to be a promising strategy to prevent the formation of AGEs.

Productos finales de glicación avanzada (AGEs) y su importancia en enfermedades crónicas relacionadas con la nutrición / Advanced glycation end products (AGEs) and its importance in chronic diseases related to nutrition

Maillard reaction occurs when reducing sugars react in a non-enzymatic way with amino groups from proteins, lipids and nucleic acids. Products of this reaction are known as Advanced Glycation End Products (AGEs). These products are formed from endogenous sources (within the body) and exogenously (produced in food preparation, as well as those supported in their formation by tobacco smoke). In the food industry this reaction is known as “browning” and is directly related to cooking time of these, affecting its color and flavor. After food preparation and the formation of exogenous AGEs, these are absorbed in the digestive tract and are part of the pool of total body AGEs. AGEs alter structure and function of molecules and increase oxidative stress in biological systems. AGEs generally refers to non-reactive terminal products as CML (3,4-Ne carboxymethyl-lysine), but alsoincludes intermediate or precursor of AGEs as 3DG (3-deoxyglucosone), or MGO (methyl -glyoxal) and its derivatives. Glycation corresponds to a non-enzymatic glycosylation. This process contributes to protein post-translational modification. This process causes quantitative and qualitative changes in the extracellular matrix components which can affect cell adhesion, growth, and others. The process of protein glycation has been associated with development mechanisms of various diseases and complications such as retinopathy, nephropathy and neuropathy associated with diabetes, macrovascular disease, Alzheimer’s disease, cataracts, and aging.

Inhibitory effect of lotus seedpod oligomeric procyanidins on advanced glycation end product formation in a lactose-lysine model system

Background Industrial food processing induces protein glycation modifications and toxic advanced glycation end products (AGEs) which affect human health. Therefore, it is of interest to monitor AGEs in food processing. The present study was carried out to investigate the influence of lotus seedpod oligomeric procyanidin (LSOPC) concentrations, solution pH value and metal ions on AGE formation by heat treatment of lactose-lysine model solutions. Ne-(carboxymethyl) lysine (CML), as one of the common AGEs was also determined by HPLC-MS/MS in this experiment. Results The results showed that LSOPC can inhibit the formation of AGEs effectively at higher concentrations, lower temperature, and it can reverse the promotion function of metal ions because of its high inhibition activity. Also, LSOPC can inhibit CML formation in the Maillard reaction as well. Conclusion These results indicated that LSOPC could be used as functional food ingredients to inhibit AGE formation.

Compositional studies and biological activities of some mash bean (Vigna mungo (L) Hepper) cultivars commonly consumed in Pakistan

BACKGROUND: In recent years, the desire to adopt a healthy diet has drawn attention to legume seeds and food products derived from them. Mash bean is an important legume crop used in Pakistan however a systematic mapping of the chemical composition of mash bean seeds is lacking. Therefore seeds of four mash bean (Vigna mungo (L.) Hepper, family Leguminoseae) cultivars (NARC-Mash-1, NARC-Mash-2, NARC-Mash-3, NARC-Mash-97) commonly consumed in Pakistan have been analyzed for their chemical composition, antioxidant potential and biological activities like inhibition of formation of advanced glycation end products (AGE) activity and tyrosinase inhibition activity. RESULTS: The investigated cultivars varied in terms of biochemical composition to various extents. Mineral composition indicated potassium and zinc in highest and lowest amounts respectively, in all cultivars. The amino acid profile in protein of these cultivars suggested cysteine is present in lowest quantity in all cultivars while fatty acid distribution pattern indicated unsaturated fatty acids as major fatty acids in all cultivars. All cultivars were found to be rich source of tocopherols and sterols. Fourier transform infrared spectroscopy (FTIR) fingerprints of seed flour and extracts indicated major functional groups such as polysaccharides, lipids, amides, amines and amino acids. Results indicated that all investigated cultivars possessed appreciable antioxidant potential. CONCLUSIONS: All cultivars are rich source of protein and possess sufficient content of dietary fiber, a balanced amino acid profile, low saturated fatty acids and antioxidant capacity that rationalizes many traditional uses of seeds of this crop besides its nutritional importance. The collected data will be useful for academic and corporate researchers, nutritionists and clinical dieticians as well as consumers. If proper attention is paid, it may become an important export commodity and may fetch considerable foreign exchange for Pakistan.

Insulinorresistencia y generación de productos finales de la glucosilación avanzada / Insulin resistance and generation of advanced glycation end products

La diabetes mellitus tipo 2 constituye una de las enfermedades más comúnmente diagnosticadas y a largo plazo lleva a diferentes complicaciones. Uno de los mecanismos por el cual se desarrollan estas alteraciones es la insulinorresistencia que impide que la glucosa sea utilizada por los diferentes órganos y tejidos, determinando alteraciones estructurales y funcionales a nivel celular. Dentro de este espectro la formación de los productos finales de la glucosilación avanzada ha alcanzado singular importancia, ya que han sido implicados en varios procesos degenerativos. Ello vuelve imperativa la necesidad de investigar potenciales blancos terapéuticos que permitan mejorar el pronóstico y la calidad de vida de los pacientes afectados por estas enfermedades.

Diabetes mellitus type 2 is one of the most frequently diagnosed diseases and in the long-term leads to a variety of complications. One of the mechanisms involved in these effects is insulin resistance which prevents glucose from being used by the different target organs and tissues, which in turn leads to structural and functional changes at the cellular level. In this context, the formation of advanced glycation end products has attained special importance as they have been implicated in several degenerative processes. It thus becomes necessary to look into potential therapeutic targets with the purpose of improving prognosis and quality of life of patients suffering from these diseases.