Oxidative stress, telomere length, and frailty in an old age population

Abstract Background A global aging population requires focusing on the risk factors for unhealthy aging, preventive medicine, and chronic disease management. The identification of adverse health outcomes in older adults has been addressed by the characterization of frailty as a biological syndrome. In this field, oxidative stress and telomere length have been suggested as biomarkers of aging Objective The objective of the study was to study the association of oxidative stress, telomere length, and frailty in an old age population Methods We conducted a cross-sectional study based on 2015 data from 202 members of a cohort of older adults (n = 202; F/M gender ratio: 133/69; mean age: 69.89 ± 7.39 years). Reactive oxygen species were measured by dichlorofluorescein diacetate and lipid peroxidation by malondialdehyde. Telomere length was determined using quantitative polymerase chain reaction with SYBR Green Master Mix Results Statistical analysis showed an association between telomere length and frailty but no association between oxidative stress and telomere length or frailty Conclusions Telomere length could eventually be used as a marker to differentiate between healthy and unhealthy aging as expressed by frailty phenotype; oxidative stress seemed merely a biological process of aging.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation / Deficiência funcional de ferro em pacientes em hemodiálise: prevalência, avaliação nutricional e de biomarcadores de estresse oxidativo e de inflamação

Abstract Introduction: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. Objectives: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. Statistical analysis: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. Results: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). Discussion: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Resumo Introdução: A anemia na DRC pode ser dividida em anemia sem deficiência funcional de ferro e com deficiência funcional de ferro (ADFF). Diante do aumento dos casos de hemossiderose em pacientes em hemodiálise, atribuídos à reposição excessiva de ferro endovenoso, maiores conhecimentos sobre os fatores envolvidos na gênese da ADFF são importantes. Objetivos: documentar a prevalência de ADFF em renais crônicos em hemodiálise. Caracterizar clínica e laboratorialmente os portadores de ADFF em HD e avaliar o estado nutricional, estresse oxidativo e inflamatório. Estudo transversal, amostra de conveniência, envolvendo 183 renais crônicos em hemodiálise no sul do Brasil. Após aplicação dos critérios de exclusão, os pacientes foram separados em dois grupos: portadores de anemia com e sem deficiência funcional de ferro. Foram submetidos a questionário socioepidemiológico, à análise antropométrica e análise laboratorial dos marcadores de anemia, estresse oxidativo, inflamatórios e nutricionais. Análise estatística: programa GraphPad InStat versão 3.1. Foram aplicados os testes: Kolmogorov-Smirnov, qui-quadrado, t de Student e Mann-Whitney. Nível de significância adotado de 5%. Resultados: não houve diferença significativa nos marcadores inflamatórios entre os dois grupos. Houve diferença significativa nos marcadores de anemia e nutrição, significativamente menores nos pacientes com ADFF. Pacientes com ADFF receberam doses mais elevadas de ferro parenteral (p < 0,05). Discussão: ADFF esteve associada a menores valores de marcadores nutricionais, mas não esteve associada a marcadores inflamatórios ou de estresse oxidativo aumentados, como relatado na literatura. Estudos adicionais sobre o tema são necessários.

Mecanismos fisiopatológicos de la sarcopenia en la EPOC / Pathophysiological mechanism of sarcopenia in COPD

La sarcopenia es una enfermedad caracterizada por la pérdida de masa muscular, fuerza muscular y rendimiento físico, siendo la principal causa de fragilidad en los adultos mayores. La sarcopenia es altamente prevalente en individuos con enfermedad pulmonar obstructiva crónica (EPOC) que conduce a un mal pronóstico y una mayor mortalidad en esta población. La presencia de sarcopenia en la EPOC es probablemente el resultado de la interacción entre factores externos e internos como la inflamación sistémica, el estrés oxidativo y los polimorfismos genéticos, frecuentemente observados en individuos con esta enfermedad respiratoria. Esta revisión resume el conocimiento sobre los mecanismos patogénicos asociados con la sarcopenia en la EPOC.

Sarcopenia is a disease characterized by loss of skeletal muscle, muscle strength and physical performance, being the major cause of frailty in the elderly. The sarcopenia is highly prevalent in individuals with Chronic obstructive pulmonary disease (COPD) leading to a poor prognosis and higher mortality in this population. The presence of sarcopenia in COPD is likely the result by the interaction between external and internal factors as systemic inflammation, oxidative stress and genetic polymorphisms, frequently observed in individuals with this respiratory disease. This review summarizes the current knowledge about the pathogenic mechanisms linking COPD with sarcopenia.

Role of native thiol, total thiol and dynamic Disulphide in diagnosis of patient with prostate cancer and prostatitis

ABSTRACT Background: Our study investigates whether Native Thiol, Total Thiol and disulphide levels measured in serum of patients with prostate cancer and prostatitis and of healthy subjects, have any role in differential diagnosis. Materials and Methods: Patients followed up for histopathologically verified diagnosis of prostate cancer and prostatitis in 2016-2017 at the Medicalpark Gaziantep Hospital Urology Clinic were included in the study. Native Thiol (NT), Total Thiol (TT), Dynamic Disulphide (DD) levels in serum were measured by a novel automated method. Results: NT, TT, DD, NT / TT ratios, DD / TT ratio and DD / NT ratio were measured as 118.4 ± 36.8μmoL / L, 150.3 ± 45.3μmoL / L, 15.9 ± 7μmoL / L, 78.8 ± 7μmoL / L, 10.5 ± 3.5μmoL / L, 13.8 ± 5.8μmoL / L respectively in patients with prostate cancer; as 116.4 ± 40.5μmoL / L, 147.5 ± 50.1μmoL / L, 15.5 ± 8.7μmoL / L, 79.7 ± 9μmoL / L, 10.1 ± 4.5μmoL / L, 13.5 ± 7.2μmoL / L in patients with prostatitis and as 144.1 ± 21.2μmoL / L, 191 ± 32.3μmoL / L, 23.4 ± 10.1μmoL / L, 76.1 ± 98.3μmoL / L, 11.9 ± 4.1μmoL / L, 16.4 ± 6.9μmoL / L in healthy subjects. Significant difference was detected between groups of NT, TT and DD levels (p = 0.008, p = 0.001, p = 0.002). No significant difference was detected in terms of the NT / TT, DD / TT and DD / NT rates (p = 0.222, p = 0.222, p = 0.222). Conclusions: Serum NT, TT, DD levels in patients with prostatitis and prostate cancer were found significantly lower compared to the control group. This indicates that just as inflammation, prostate cancer also increases oxidative stress on tissues.

Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox Imbalance and Inflammation / Doença Renal do Diabetes: Cross-Linking entre Hiperglicemia, Desequilíbrio Redox e Inflamação

Abstract Chronic hyperglycemia is the key point of macro- and microvascular complications associated with diabetes mellitus. Excess glucose is responsible for inducing redox imbalance and both systemic and intrarenal inflammation, playing a critical role in the pathogenesis of diabetic kidney disease, which is currently the leading cause of dialysis in the world. The pathogenesis of the disease is complex, multifactorial and not fully elucidated; many factors and mechanisms are involved in the development, progression and clinical outcomes of the disease. Despite the disparate mechanisms involved in renal damage related to diabetes mellitus, the metabolic mechanisms involving oxidative/inflammatory pathways are widely accepted. The is clear evidence that a chronic hyperglycemic state triggers oxidative stress and inflammation mediated by altered metabolic pathways in a self-perpetuating cycle, promoting progression of cell injury and of end-stage renal disease. The present study presents an update on metabolic pathways that involve redox imbalance and inflammation induced by chronic exposure to hyperglycemia in the pathogenesis of diabetic kidney disease.

Resumo A hiperglicemia crônica é o ponto-chave das complicações macro e microvasculares associadas ao diabetes mellitus. O excesso de glicose é responsável por induzir desequilíbrio redox e inflamação sistêmica e intra-renal, desempenhando um papel crítico na patogênese da doença renal do diabetes, configurada atualmente como a principal causa de doença renal dialítica em todo o mundo. A patogênese da doença é complexa, multifatorial e, não totalmente elucidada, estando vários fatores e mecanismos associados ao seu desenvolvimento, progressão e desfechos clínicos. Apesar dos mecanismos díspares envolvidos nos danos renais durante o diabetes, os caminhos metabólicos pela via oxidativa/inflamatória são amplamente aceitos e discutidos. As evidências acentuam que o estado hiperglicêmico crônico desencadeia o estresse oxidativo e a inflamação mediada por diversas vias metabólicas alteradas em um ciclo-vicioso de autoperpetuação, promovendo aumento da injúria celular e progressão para a doença renal dialítica. O presente artigo traz, portanto, uma atualização sobre os caminhos metabólicos que envolvem o desequilíbrio redox e a inflamação induzidos pela exposição crônica à hiperglicemia na patogênese da doença renal do diabetes.

Oxidative stress effects in the uterus, placenta and fetus of pregnant rats submitted to acute and chronic stress

Abstract Purpose: To evaluate the effects of oxidative stress in pregnant rats submitted to acute and chronic stress, relating to alterations in the uterus, placenta and fetus. Methods: Twenty-four female Wistar albino (Rattus norvegicus), were divided into four groups, for induction of oxidative stress the animals were submitted to cold and physical immobilization. Plasma fasting glucose and MDA were determined in all groups and the fetuses and placentas were measured. Results: There were no statistical differences in the levels of malonic dialdehyde (MDA), however the averages of chronic stress group were higher compared to control groups, which could explain the observed adverse effects; there was no correlation between puppies' size, the weight of the placenta and MDA values. Conclusions: Chronic stress causes adverse effects, when compared to control groups; chronic stress group had fetuses, placentas and number of puppies, significantly lower compared to other groups. The rats exposed to chronic stress, also presented a higher frequency of fetal resorption.

Oxidative stress and immune system analysis after cycle ergometer use in critical patients

OBJECTIVE: The passive cycle ergometer aims to prevent hypotrophy and improve muscle strength, with a consequent reduction in hospitalization time in the intensive care unit and functional improvement. However, its effects on oxidative stress and immune system parameters remain unknown. The aim of this study is to analyze the effects of a passive cycle ergometer on the immune system and oxidative stress in critical patients. METHODS: This paper describes a randomized controlled trial in a sample of 19 patients of both genders who were on mechanical ventilation and hospitalized in the intensive care unit of the Hospital Agamenom Magalhães. The patients were divided into two groups: one group underwent cycle ergometer passive exercise for 30 cycles/min on the lower limbs for 20 minutes; the other group did not undergo any therapeutic intervention during the study and served as the control group. A total of 20 ml of blood was analysed, in which nitric oxide levels and some specific inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and interleukins 6 (IL-6) and 10 (IL-10)) were evaluated before and after the study protocol. RESULTS: Regarding the demographic and clinical variables, the groups were homogeneous in the early phases of the study. The nitric oxide analysis revealed a reduction in nitric oxide variation in stimulated cells (p=0.0021) and those stimulated (p=0.0076) after passive cycle ergometer use compared to the control group. No differences in the evaluated inflammatory cytokines were observed between the two groups. CONCLUSION: We can conclude that the passive cycle ergometer promoted reduced levels of nitric oxide, showing beneficial effects on oxidative stress reduction. As assessed by inflammatory cytokines, the treatment was not associated with changes in the immune system. However, further research in a larger population is necessary for more conclusive results.

Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration

Although acute exercise is apparently pro-inflammatory and increases oxidative stress, it can promote the necessary stress stimulus to train chronic adaptations in patients with chronic heart failure (CHF). This study aimed to compare the effects of exercise intensity and duration on the inflammatory markers soluble tumor necrosis factor receptor (sTNFR1) and interleukin-6 (IL-6), and on oxidative stress [malondialdehyde (MDA) and antioxidant enzymes: catalase (CAT) and superoxide dismutase (SOD)] in individuals with CHF. Eighteen patients performed three exercise sessions: 30 min of moderate-intensity (M30) exercise, 30 min of low-intensity (L30) exercise, and 45 min of low-intensity (L45) exercise. Blood analysis was performed before exercise (baseline), immediately after each session (after), and 1 h after the end of each session (1h after). Thirty min of M30 exercise promoted a larger stressor stimulus, both pro-inflammatory and pro-oxidative, than that promoted by exercises L30 and L45. This was evidenced by increased sTNFR1 and MDA levels after exercise M30. In response to this stressor stimulus, 1 h after exercise, there was an increase in IL-6 and CAT levels, and a return of sTNFR1 to baseline levels. These findings suggest that compared with the duration of exercise, the exercise intensity was an important factor of physiologic adjustments.

Peripheral brain-derived neurotrophic factor is related to cardiovascular risk factors in active and inactive elderly men

Regular exercise plays an important preventive and therapeutic role in heart and vascular diseases, and beneficially affects brain function. In blood, the effects of exercise appear to be very complex and could include protection of vascular endothelial cells via neurotrophic factors and decreased oxidative stress. The purpose of this study was to identify the age-related changes in peripheral brain-derived neurotrophic factor (BDNF) and its relationship to oxidative damage and conventional cardiovascular disease (CVD) biomarkers, such as atherogenic index, C-reactive protein (hsCRP) and oxidized LDL (oxLDL), in active and inactive men. Seventeen elderly males (61-80 years) and 17 young males (20-24 years) participated in this study. According to the 6-min Åstrand-Rhyming bike test, the subjects were classified into active and inactive groups. The young and elderly active men had a significantly better lipoprotein profile and antioxidant status, as well as reduced oxidative damage and inflammatory state. The active young and elderly men had significantly higher plasma BDNF levels compared to their inactive peers. BDNF was correlated with VO2max (r=0.765, P<0.001). In addition, we observed a significant inverse correlation of BDNF with atherogenic index (TC/HDL), hsCRP and oxLDL. The findings demonstrate that a high level of cardiorespiratory fitness reflected in VO2max was associated with a higher level of circulating BDNF, which in turn was related to common CVD risk factors and oxidative damage markers in young and elderly men.

INFLUENCE OF OXIDATIVE STRESS AND OBESITY IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS / Influência do estresse oxidativo e obesidade em pacientes com esteatohepatite não alcoólica

BackgroundNonalcoholic steatohepatitis is considered the hepatic manifestation of metabolic syndrome and it is particularly associated to the insulin resistance, hypertension, obesity and abnormalities in lipid and glucose metabolism.ObjectiveConsidering the importance of obesity and oxidative stress in the pathophysiology of nonalcoholic steatohepatitis, this study aimed to evaluate the presence and association of the obesity and oxidative stress in this pathology.MethodsFifteen outpatients with nonalcoholic steatohepatitis (nonalcoholic steatohepatitis group), diagnosed according to the histopathological findings from the liver biopsy, and 15 body mass index-matched subjects (non nonalcoholic steatohepatitis group) without nonalcoholic steatohepatitis were included. All volunteers were registered in a Brazilian University Hospital. Nutritional assessment (weight, height, body mass index and waist circumference) and biochemical analysis (fasting glucose, liver enzymes, lipid profile, leptin, superoxide dismutase, glutathione peroxidase, vitamins C and E, catalase and 8-isoprostane) were performed for all the participants. The student t test was used for statistical analysis, with P<0.05 as the significant factor.ResultsNonalcoholic steatohepatitis patients had higher fasting glucose, hepatic enzymes (serum aspartate aminotransaminase, alanine aminotransaminase, gamma glutamyl transferase, alkaline phosphatase), triglycerides and superoxide dismutase and lower glutathione peroxidase values than non nonalcoholic steatohepatitis individuals.ConclusionThis paper demonstrates that only the presence of obesity is not enough to trigger alterations in all the studied biomarkers. Despite the majority of oxidative stress markers being found to be similar in both conditions, the nonalcoholic steatohepatitis subjects could be slightly more affected than the non nonalcoholic steatohepatitis individuals.

ContextoEsteatohepatite não alcoólica é considerada uma manifestação hepática da síndrome metabólica e está particularmente associada com a resistência insulínica, hipertensão, obesidade, anormalidades no metabolismo lipídico e da glicose.ObjetivoConsiderando a importância da obesidade e do estresse oxidativo na fisiopatogenia da esteatohepatite não alcoólica, o objetivo deste estudo foi avaliar a associação e presença da obesidade e do estresse oxidativo nesta patologia.MétodosQuinze pacientes com esteatohepatite não alcoólica (grupo esteatohepatite não alcoólica), diagnosticados de acordo com os achados histopatológicos da biópsia hepática, e 15 indivíduos sem esteatohepatite não alcoólica com sobrepeso/obesidade (grupo sem esteatohepatite não alcoólica) foram incluídos. Todos os voluntários eram acompanhados em Hospital Universitário Brasileiro. Avaliação nutricional (peso, altura, índice de massa corporal e circunferência abdominal) e bioquímica (glicemia de jejum, enzimas hepáticas, lipidograma, leptina, superóxido dismutase, glutationa peroxidase, vitaminas C e E, catalase e 8-isoprostano) foram realizadas em todos os indivíduos. O teste t de Student foi usado para análise estatística considerando o P≤0,05 como significativo.ResultadosIndivíduos do Grupo esteatohepatite não alcoólica apresentaram valores significativamente maiores de glicemia, AST, ALT, Gama GT, fosfatase alcalina, triglicérides e superóxido dismutase e menor valor de glutationa peroxidase, quando comparados ao Grupo sem esteatohepatite não alcoólica.ConclusãoEste artigo demonstra que somente a presença da obesidade não é suficiente para provocar alterações nos biomarcadores estudados. Apesar da maioria dos marcadores de estresse oxidativo apresentarem-se similar nas duas condições, os pacientes com esteatohepatite não alcoólica podem apresentar-se levemente mais afetados que os indivíduos sem esteatohepatite não alcoólica.

Superoxide overproduction and kidney fibrosis: a new animal model / Produção aumentada de superóxido e fibrose renal: novo modelo animal

Objective To establish whether the mutation in the Immp2L gene induces renal fibrosis and whether aging exacerbates renal morphology in mice. Methods Female mutant mice with mutation in the inner mitochondrial membrane peptidase 2-like protein at 3 and 18 months of age were used. Renal fibrosis was analyzed using classic fibrosis score, Masson’s trichrome staining, and analysis of profibrotic markers using real time polymerase chain reaction (superoxide dismutase 1, metalloproteinase-9, erythropoietin, transforming growth factor beta), and immunostaining (fibroblasts and Type IV collagen). Oxidative stress markers were determined by immunohistochemistry. The number of renal apoptotic cells was determined. Renal function was estimated by serum creatinine. Results Young mutant mice had significantly more glomerulosclerosis than age-matched mice (p=0.034). Mutant mice had more tubular casts (p=0.025), collagen deposition (p=0.019), and collagen type IV expression (p<0.001). Superoxide dismutase 1 expression was significantly higher in young mutants (p=0.038). Old mutants exhibited significantly higher expression of the fibroblast marker and macrophage marker (p=0.007 and p=0.012, respectively). The real time polymerase chain reaction of metalloproteinase-9 and erythropoietin were enhanced 2.5- and 6-fold, respectively, in old mutants. Serum creatinine was significantly higher in old mutants (p<0.001). Conclusion This mutation altered renal architecture by increasing the deposition of extracellular matrix, oxidative stress, and inflammation, suggesting a protective role of Immp2L against renal fibrosis. .

Objetivo Estabelecer se a mutação no gene Immp2L induz à fibrose renal e se o envelhecimento exacerba a morfologia renal em camundongos. Métodos Foram usadas fêmeas de camundongos mutantes para proteína semelhante à peptidase 2 da camada interna da mitocôndria, com 3 e 18 meses de idade. Para analisar a fibrose renal, foram usados o escore clássico de fibrose, a coloração com tricrômio de Masson, e a análise de marcadores profibróticos, por meio da reação em cadeia de polimerase em tempo real (superóxido dismutase 1, metalonoproteinase-9, eritropoietina e fator transformador de crescimento beta), e a imunocoloração (fibroblastos e colágeno IV). Marcadores de estresse oxidativo foram determinados por imuno-histoquímica. O número de células apoptóticas renais foi analisado. A função renal foi estimada por creatinina sérica. Resultados Camundongos mutantes jovens apresentaram glomeruloesclerose em quantidade significativamente maior que animais da mesma idade (p=0,034). Os mutantes mostraram maior formação de cilindros tubulares (p=0,025), deposição de colágeno (p=0,019) e maior expressão de colágeno do tipo IV (p<0,001). A expressão de superóxido dismutase 1 foi maior em mutantes jovens (p=0,038). Mutantes idosas exibiram maior expressão dos marcadores de fibroblastos e macrófagos (p=0,007 e p=0,012, respectivamente). As reações da cadeia de polimerase em tempo real da metalanoproteinase-9 e da eritropoietina estavam aumentadas em 2,5 e 6 vezes, respectivamente, em mutantes idosas. A creatinina sérica foi significantemente maior em animais idosos mutantes (p<0,001). Conclusão Essa mutação alterou a arquitetura renal pelo aumento da deposição de matriz extracelular, estresse oxidativo e inflamação, sugerindo papel de proteção de Immp2L contra a fibrose renal. .

Oxidative stress and plasma lipoproteins in cancer patients / Estresse oxidativo e lipoproteínas plasmáticas em pacientes com câncer

Objective To evaluate the relation between oxidative stress and lipid profile in patients with different types of cancer. Methods This was an observational cross-sectional. A total of 58 subjects were evaluated, 33 males, divided into two groups of 29 patients each: Group 1, patients with cancer of the digestive tract and accessory organs; Group 2 patients with other types of cancers, all admitted to a public hospital. The plasma levels (lipoproteins and total cholesterol, HDL, and triglycerides, for example) were analyzed by enzymatic kits, and oxidative stress based on thiobarbituric acid-reactive substances, by assessing the formation of malondialdehyde. Results In general the levels of malondialdehyde of patients were high (5.00μM) as compared to 3.31μM for healthy individuals. The median values of lipids exhibited normal triacylglycerol (138.78±89.88mg/dL), desirable total cholesterol values (163.04±172.38mg/dL), borderline high LDL (151.30±178.25mg/dL) and low HDL (31.70±22.74mg/dL). Median HDL levels in Group 1 were lower (31.32mg/dL) than the cancer patients in Group 2 (43.67mg/dL) (p=0.038). Group 1 also showed higher levels of oxidative stress (p=0.027). Conclusion The lipid profile of patients with cancer was not favorable, which seems to have contributed to higher lipid peroxidation rate, generating a significant oxidative stress. .

Objetivo Avaliar a relação entre estresse oxidativo e perfil lipídico em pacientes com diferentes tipos de câncer. Métodos Estudo do tipo observacional transversal. Foram avaliados 58 indivíduos, sendo 33 do sexo masculino, divididos em dois grupos de 29 pacientes cada: o Grupo 1 foi formado por pacientes com câncer do trato digestivo e órgãos anexos; o Grupo 2 foi formado por pacientes com outros tipos de câncer, todos internados em um hospital público. Foram analisadas concentrações plasmáticas (colesterol total, HDL e triacilglicerol, entre outras), por meio de kits enzimáticos, e o estresse oxidativo, com base em substâncias reativas ao ácido tiobarbitúrico, por meio da formação de malondialdeído. Resultados Na mediana, os pacientes apresentaram valores altos de malondialdeído (5,00μM) quando comparados ao valor de 3,31μM para indivíduos saudáveis. A mediana do perfil lipídico exibiu valores de triacilgliceróis normais (138,78±89,88mg/dL), colesterol total com valores desejáveis (163,04±172,38mg/dL), LDL com limiar elevado (151,30±178,25mg/dL) e HDL baixo (31,70±22,74mg/dL). Os níveis medianos de HDL do Grupo 1 foram mais baixos (31,32mg/dL) do que dos pacientes oncológicos do Grupo 2 (43,67mg/dL) (p=0,038). O Grupo 1 apresentou níveis mais altos de estresse oxidativo (p=0,027). Conclusão O perfil lipídico de pacientes com câncer apresentou-se desfavorável, o que parece ter contribuído para uma maior taxa de peroxidação lipídica, gerando um significativo estresse oxidativo. .

Marcadores de estrés oxidativo y su relación con el estado nutricional en adultos, Ecuador / Relationships between biomarkers of oxidative stress and nutritional status in adults, Ecuador

Se evaluó la relación entre biomarcadores de estrés oxidativo (ácido úrico, bilirrubina y proteína C-reactiva) con el estado nutricional en 321 adultos de Ecuador, pertenecientes al personal administrativo de la Universidad Técnica del Norte, con edades de 43 ± 10 años, (46,30% femenino y 53,61% masculino). Se obtuvo información sociodemográfica, de estilo de vida y epidemiológica; se calculó el índice de Masa Corporal (IMC), porcentaje de grasa y agua corporal, se midió la circunferencia de la cintura (CC) y la presión arterial y se determinó las concentraciones de ácido úrico, bilirrubina y Proteína C reactiva (PCR). Se encontró que 17,9% de la población presentó obesidad y 51,72% sobrepeso. Los valores más elevados de ácido úrico se encontraron en obesos, hipertensos y en quienes realizan actividad física. La bilirrubina total, directa e indirecta se encontró en límites superiores en los grupos con obesidad abdominal, y con actividad física. Las variables % de grasa y de agua influyen en la PCR en el grupo con baja grasa corporal y en las mujeres. En hombres, la PCR se asocia con IMC y CC. En los grupos sobrepeso, alta grasa corporal y PHT, el ácido úrico mostró relación con el % de grasa y la CC En los obesos con el % de agua e IMC y en los grupos obesidad abdominal e HT se asoció con % de agua y CC Se concluye que el porcentaje de agua corporal es un importante indicador nutricional para el desarrollo de estrés oxidativo en esta población.

In this work it was evaluated the relationship between oxidative stress biomarkers (uric acid, bilirubin and C-reactive protein) with nutritional status in 321 adults of Ecuador, belonging to administrative staff of of the Universidad Tècnica del Norte , aged 43 ± 10 years old (46 30% female and 53.61% male). Socio demographic and epidemiological information and lifestyle were obtained through a survey; The Body Mass Index (BMI) and body fat and body water percentages were calculated; waist circumference (WC) and blood pressure was measured. Determinations of uric acid, bilirubin, and serum C-reactive protein (PCR) were performed. 17.9% of the populations were obese and 51.72% overweight. The highest values of uric acid were found in obese, hypertensive and physical activity groups. The total direct and indirect bilirubin were found in upper limits in abdominal obesity and physical activity groups. The CRP level was influenced by % fat and % water in the low body fat group and in females. In male, BMI and WC were associated with CRP. Uric acid showed relationship with % fat and WC in overweight, high body fat and PHT groups, uric acid was associated with the % water and BMI in obese. Finally, uric acid was associated with % water and the WC in the abdominal obesity, and HT groups' .The body water percentage is an important indicator to development of oxidative stress in this population.

Papel de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal / Mitochondria and oxidative stress participation in renal inflammatory process

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.

The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

Dietas ricas em gordura, frutose e sacarose: alterações no fígado / Diets high in fat, fructose and sucrose: changes in liver

Hábitos inadequados no estilo de vida, pelo consumo exacerbado de dietas ricas em gorduras e açúcares (frutose e sacarose), correlacionam-se positivamente com o desenvolvimento da obesidade, da resistência à insulina (RI) e da esteatose hepática não alcoólica (NAFLD). O estudo teve como objetivo avaliar a magnitude dos efeitos da administração crônica de dietas ricas em gordura e/ou frutose, e ainda, comparar os efeitos dos açúcares isoladamente (frutose e sacarose) sob as alterações bioquímicas, o perfil inflamatório, as respostas morfofuncionais e as expressões proteicas e gênicas de fatores de transcrição envolvidos na lipogênese, na beta-oxidação, na gliconeogênese e no estresse oxidativo no fígado. Camundongos machos C57BL/6 foram divididos em dois experimentos: 1) Dieta controle/standard chow (SC), dieta high fat (HF – 42%), dieta high frutose (HFr – 34%) e dieta high fat + high frutose (HFHFr - 42% fat + 34% frutose) por 16 semanas; 2) Dieta controle/standard chow (SC), dieta high frutose (HFru – 50%) e dieta high sacarose (HSu – 50%) por 15 semanas. Ao final dos experimentos foram observados: 1) Não houve diferença na massa corporal entre os animais HFr e SC, só foi observado ganho de peso nos grupos HF e HFHFr. Houve ainda aumento do colesterol total, dos triglicerídeos plasmáticos e hepáticos e RI nos grupos HF, HFr e HFHFr. No fígado, foi observado NAFLD com aumento na expressão de SREBP-1c e PPAR-γ, e redução de PPAR-α. A gliconeogênese mediada pelo GLUT-2 e PEPCK também foi aumentada nos grupos HF, HFr e HFHFr em relação ao grupo SC. Áreas de necroinflamação também foram observadas nos animais HFr e HFHFr; 2) Não houve diferença na massa corporal entre os grupos SC, HFru e HSu. Porém, houve aumento do colesterol total, dos triglicerídeos plasmáticos e hepáticos, da RI, das adipocinas (IL-6, resistina, MCP-1 e leptina), e redução da adiponectina...

Habits unsuitable lifestyle, exacerbated by consumption of diets rich in fat and sugars (sucrose and fructose) are positively correlated with the development of obesity, insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The study aimed to evaluate the magnitude of the effects of chronic administration of diets rich in fat and/or fructose, and also compare the effects of sugars alone (fructose and sucrose) in the biochemical changes, the inflammatory profile, and the morphological and functional responses the protein and gene expression of transcription factors involved in lipogenesis, beta-oxidation, gluconeogenesis and oxidative stress in the liver. Male C57BL / 6 mice were divided into two experiments: 1) Diet control/standard chow (SC), high fat diet (HF - 42%), high-fructose diet (HFr - 34%) and high fat + high fructose diet (HFHFr - 42% fat + 34% fructose) for 16 weeks; 2) Diet control/standard chow (SC), high-fructose diet (HFru - 50%) and high sucrose diet (HSu - 50%) for 15 weeks. At the end of the experiments were observed: 1) There was no difference in body mass between HFr and SC groups, only weight gain was observed in the HF group and HFHFr. There was also an increase in total cholesterol, plasma and hepatic triglycerides and IR in HF, HFr, HFHFr groups. In the liver, NAFLD was observed with increased expression of SREBP-1c, PPAR-γ and PPAR-α reduction. The gluconeogenesis mediated by GLUT-2 and PEPCK was also increased in HF, HFr and HFHFr groups compared to SC. Areas of necroinflammation were also observed in HFr and HFHFr; 2) There was no difference in body mass between the SC, HFru and HSu groups. However, there was an increase in total cholesterol, plasma and hepatic triglycerides, IR, adipokines (IL-6, resistin, leptin and MCP-1), and decreased of adiponectin...

Efecto del extracto acuoso de la raíz de Ruellia Tuberosa L. sobre el daño renal en la diabetes. Papel del estrés oxidativo / Effect of the aqueous extract of the root of Ruellia Tuberosa L. on kidney damage in diabetes. Role of oxidative stress

La diabetes es una de los principales problemas de la salud pública mundial, en parte debido a su asociación con otras enfermedades cardiometabólicas. Las complicaciones tisulares de la diabetes es su principal causa de muerte, siendo la nefropatía diabética la que lidera la lista de daños inducidos por la hiperglicemia crónica. Se conocen varios mediadores celulares de la nefropatía: la angiotensina II, los productos de glicosilación avanzada, las kinasas activadas por mitógenos, las especies reactivas de oxígeno y nitrógeno, entre otras, cuya activación traen como consecuencia el aumento de la síntesis de proteínas de la matriz extracelular, el ensanchamiento del glomérulo, el daño tubular y la fibrosis. Esto se traduce en insuficiencia renal crónica, caracterizada por la proteinuria, el aumento de la diuresis, el desequilibrio electrolítico, el incremento de creatinina plasmática y del nitrógeno ureico en sangre (BUN), los cuales son considerados marcadores clínicos del daño renal en la diabetes. Muchos grupos de investigación están enfocados en la búsqueda de fármacos que sean capaces de abolir, disminuir o prevenir la nefropatía diabética. En el campo de la etnobotánica, la etnomedicina y la etnofarmacología existen diversos estudios que han aportado nuevas especies, fitofármacos y productos naturales para el tratamiento no sólo de la diabetes, sino también de sus complicaciones. Existen alrededor de 1200 plantas antidiabéticas en el mundo. En Venezuela son muy pocas las especies que han sido estudiadas, a pesar que goza de gran biodiversidad vegetal. Ruellia tuberosa L. (yuquilla) es una de estas plantas de uso etnomédico, la cual pertenece a la familia Acanthaceae y está distribuida en todo el país. Las partes aéreas de esta especie han sido estudiadas de manera exhaustiva, encontrándose actividad: antidiabética, antioxidante, antiinflamatoria y analgésica. Sin embargo, su raíz ha sido muy poco estudiada. Recientemente, reportamos la actividad analgésica y antiinflamatoria del extracto acuoso de la raíz de R. tuberosa (RT) en animales de experimentación. Con el fin de validar su uso tradicional como antidiabético y de conocer la capacidad protectora ante las complicaciones de la diabetes, en este trabajo se evaluó el efecto del RT sobre el daño renal en un modelo de ratas con diabetes inducida por la estreptozotocina (ETZ) e in vitro en células de epitelio renal (células Vero) sometidas a altas concentraciones de glucosa. Asimismo, se evaluó la relación de la actividad protectora del RT con su potencial antioxidante y con la inhibición de la vía de señalización de la PKC-NF-κB. Para ello fueron evaluadas las modificaciones de la glicemia, de los marcadores de daño renal, el daño oxidativo renal, el sistema antioxidante renal, la proliferación y muerte de las células de epitelio renal, en los modelos experimentales bajo diferentes condiciones de estrés. Asimismo la expresión del NF-κB inducida por un activador de la PKC (PMA) en células de cáncer de cuello uterino (HeLa), la actividad antioxidante y el contenido de polifenoles del extracto. Los resultados muestran que el RT contiene compuestos polifenólicos y que produce un efecto atrapador del anión superóxido, estableciéndose así su capacidad antioxidante. El RT disminuyó la glicemia, la proteinuria, la diuresis, el BUN la creatinina plasmática y la pérdida de peso en los animales diabéticos; disminuyó el contenido de grupos carbonilos en las proteínas, de malonildialdehido, de proteínas totales en la corteza renal y suprimió el incremento del peso del riñón en las ratas con diabetes inducida por la ETZ; contrarrestó el decremento de la actividad de la CAT, SOD total, CuZn-SOD, GPx y GR inducida por la glucosa in vivo e in vitro; protegió a las células Vero de la glucotoxicidad, del estrés oxidativo y del estrés nitrosativo, inducido por la alta glucosa, por el peróxido de hidrógeno y por el nitroprusiato de sodio respectivamente. Sin embargo, el peróxido, el nitroprusiato así como el PMA disminuyeron el efecto protector del RT sobre la glucotoxicidad. Este extracto previno el incremento de la actividad del NF-κB inducido por el PMA en las células HeLa. Todos estos hallazgos establecen al RT como un antioxidante con efecto protector sobre el daño renal en la diabetes, tanto in vivo como in vitro, a través de un mecanismo que involucra la disminución de la glicemia, del estrés oxidativo, del estrés nitrosativo, y de la vía de señalización de la PKC-NF-kB. Esto aporta, por primera vez, información acerca de los efectos farmacológicos de la especie, a la vez que contribuye tanto a la validación de su uso tradicional como a la caracterización farmacológica de su género, sentado así las bases para el estudio fitoquímico y tecnológico de este potencial fitofármaco.

O envolvimento do estresse oxidativo e nitrosativo em modelo de doença pulmonar obstrutiva crônica (DPOC) induzido por elastase / The involvement of oxidative and nitrosative stress in model of chronic obstructive pulmonary disease (COPD) induced by elastase

Este estudo buscou investigar o papel do estresse oxidativo e nitrosativo no enfisema pulmonar induzido por elastase. Foram utilizados camundongos machos C57BL/6 submetidos a dois modelos de indução do enfisema por elastase pancreática suína (PPE): intratraqueal (i.t.) e intranasal (i.n.). No modelo intratraqueal a PPE foi instilada nas doses de 0,05 U ou 0,05 U/camundongo para avaliação temporal do enfisema 7, 14 e 21 dias após instilação de PPE. Em outra etapa, o papel da iNOS foi avaliado através da sua inibição farmacológica por aminoguanidina (AMG) 1% na água de beber ou pela sua exclusão genética em camundongos deficientes em iNOS que tiveram o enfisema induzido por 0,5 U PPE i.t. após 21 dias. No modelo intranasal a dose de PPE foi 3 U/camundongo para avaliação temporal do enfisema (1, 7, 14 e 21 dias após PPE). O papel do estresse oxidativo e nitrosativo foi avaliado com diferentes tratamentos antioxidantes na água de beber: tempol, apocinina+alopurinol, n-acetilcisteína, vitamina C+E, e aminoguanidina durante os 21 dias de indução do enfisema. Os grupos controles foram submetidos à instilação de salina. Lavado broncoalveolar, imunoensaios, análises bioquímicas de estresse oxidativo e ensaios morfométricos foram realizados nos pulmões dos animais. O enfisema foi histologicamente alcançado em 21 dias após 0,5 U PPE i.t., evidenciado pelo aumento do diâmetro alveolar médio - Lm e da densidade de volume dos espaços alveolares - Vvair em comparação ao grupo controle. TNF-a foi aumentado em 7 e 14 dias após 0,05 U PPE comparados ao controle, concomitante com a redução de IL-10 nos mesmos períodos, comparados ao controle. O estresse oxidativo foi observado na fase inicial do enfisema, com aumento dos níveis de nitrito, TBARS e superóxido dismutase no grupo 7 dias após 0,5 U PPE (i.t.) quando comparados ao controle ao passo que no modelo intranasal as alterações típicas do estresse foram vistas no grupo 1 dia após 3 U de PPE. Atividade da glutationa ...

This study investigated the role of oxidative and nitrosative stress in elastase-induced pulmonary emphysema. C57BL/6 male mice were used submitted to two models of emphysema induced by porcine pancreatic elastase (PPE): intratracheal (i.t.) and intranasal (i.n.). In the intratracheal model PPE was instilled at doses of 0.05 U or 0.5 U/mouse (i.t.) to temporal evaluation of emphysema 7, 14 and 21 days post-PPE instillation. Others sets of experiments, the role of iNOS was evaluated through its pharmacology inhibition by 1% aminoguanidine (AMG) into the drinking water or bt iNOS genetic exclusion in iNOS-deficient mice which had induced emphysema by 0.5 U PPE i.t. after 21 days. In the intranasal model the PPE dose was 3 U/mouse to temporal evaluation of emphysema (1, 7, 14 and 21 days after PPE). The role of oxidative and nitrosative stress was evaluated using different antioxidant treatments into the drinking water: tempol, apocynin+allopurinol, N-acetylcysteine, vitamin C+E and aminoguanidine during the 21 days of emphysema induction. Control groups were instilled with saline. Bronchoalveolar lavage, immunoassays, biochemical analysis of oxidative stress and morphometric tests were performed in the lungs of animals. The emphysema was histologically reached 21 days after 0.5 U PPE, as evidenced by an increase in alveolar diameter - Lm and volume density of the alveolar spaces - Vvair compared to the control group. TNF-a was increased in 7 and 14 days after 0.5 U PPE compared to the control, concomitant with reduction of IL-10 at the same time-points compared to the control. Oxidative stress was observed in the early stages of emphysema, with increased levels of nitrite, TBARS and superoxide dismutase in group 7 days after 0.5 U PPE (i.t.) compared to the control, while in the intranasal model the typical stress alterations were seen in group 1 day after 3 U PPE. Glutathione peroxidase activity was increased in all PPE groups (i.t.). Exposure to 0.5 U PPE ...

Ácido úrico: una molécula con acciones paradójicas en la insuficiencia cardiaca / The role of uric acid in heart failure

Complications and mortality of heart failure are high, despite the availability of several forms of treatment. Uric acid, the end product of purine metabolism would actively participate in the pathophysiology of heart failure. However, there is no consensus about its action in cardiovascular disease. Serum uric acid would have a protective antioxidant activity. This action could help to reduce or counteract the processes that cause or appear as a result of heart failure. However, these protective properties would vanish in the intracellular environment or in highly hydrophobic areas such as atherosclerotic plaques and adipose tissue. This review discusses the paradoxical action of uric acid in the pathophysiology of heart failure.

Lipid profile, apolipoprotein A-I and oxidative stress in professional footballers, sedentary individuals, and their relatives / Perfil lipídico, apolipoproteína A-I e estresse oxidativo em jogadores de futebol profissionais, indivíduos sedentários e seus familiares

OBJECTIVE: To evaluate whether lipid profile (LP), apolipoprotein A-1 (apo A-I) and malondialdehyde (MDA) have any relationship with physical exercise by comparing the groups of footballers (FG) with sedentary individuals (CG) and their relatives (RFG and RCG). SUBJECTS AND METHODS: Twenty individuals from FG and CG, 60 from RFG, and 57 from RCG were studied. RESULTS: FG showed lower levels of total cholesterol (119.5 ± 37.9 mg/dL), LDL-cholesterol fraction (53.6 ± 30.3), apo A-I (116.7 ± 11.9), and higher level of HDL-cholesterol fraction (HDLc) (49.7 ± 8.5) compared to RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; and 42.7 ± 7.7, P < 0.01; respectively). Moreover, FG had reduced levels of MDA (101.0 ± 77.0 ng/mL) compared to CG (290.0 ± 341.0, P = 0.03) and RFG (209.9 ± 197.5, P = 0.04). CONCLUSIONS: These results suggest an association between physical exercise and lower levels of MDA in FG. Physical activity seems to promote beneficial effects on the LP regardless of the genetic influence considering HDLc levels.

OBJETIVO: Avaliar se perfil lipídico (PL), apolipoproteína A-1 (apo A-I) e malondialdeído (MDA) têm relação com atividade física comparando os grupos: jogadores de futebol (FG) com indivíduos sedentários (CG) e seus familiares. SUJEITOS E MÉTODOS: Foram avaliados 20 indivíduos de FG e CG, além de 60 familiares de FG (RFG) e 57 de CG (RCG). RESULTADOS: FG mostrou menores níveis (média ± DP [mg/dL]) de colesterol total (119.5 ± 37.9), LDL colesterol (53.6 ± 30.3), e apo A-I (116.7 ± 11.9), e maiores níveis de HDL colesterol (HDLc) (49.7 ± 8.5) comparado ao RFG (148.3 ± 36.9, P = 0.02; 82.4 ± 37.7, P < 0.01; 124.6 ± 10.2, P = 0.03; e 42.7 ± 7.7, P < 0.01; respectivamente). Além disso, o FG mostrou níveis reduzidos de MDA (101.0 ± 77.0 [ng/mL]) comparado a CG (290.0 ± 341.0, P = 0.03) e RFG (209.9 ± 197.5, P = 0.04). CONCLUSÕES: Esses resultados sugerem que existe uma associação entre atividade física e níveis reduzidos de MDA em FG. O exercício físico parece promover efeitos benéficos no PL independente da influência genética considerando os níveis de HDLc.

O papel do estresse oxidativo na DPOC: conceitos atuais e perspectivas / The role of oxidative stress in COPD: current concepts and perspectives

A DPOC é uma causa importante de morbidade e mortalidade em escala global. As manifestações clínicas e funcionais da DPOC resultam de danos pulmonares provocados por um conjunto de mecanismos, incluindo o estresse oxidativo, a inflamação, o desequilíbrio do sistema protease-antiprotease e a apoptose. O estresse oxidativo é central na gênese da DPOC, pois além de provocar dano direto às estruturas pulmonares, amplifica os demais mecanismos. Os eventos celulares e moleculares responsáveis pelo dano pulmonar antecedem em muito a expressão clínica e funcional da DPOC. Os broncodilatadores, principais drogas empregadas atualmente no tratamento da DPOC, não são eficazes em reduzir a progressão da doença. Avanços na compreensão da patogênese da DPOC aliados a esforços renovados na pesquisa básica e clínica deverão permitir sua detecção na fase pré-clínica e possibilitar um monitoramento mais adequado de sua atividade, além de permitir a introdução de novas modalidades de agentes terapêuticos capazes de impedir eficazmente sua progressão.

Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more appropriate monitoring of disease activity, as well as leading to the development of novel therapeutic agents that will effectively prevent the progression of the disease.