The role of antioxidants in the chemistry of oxidative stress: A review.

Oxidative stress and chronic inflammation are known to be associated with the development of metabolic diseases, including diabetes. Oxidative stress, an imbalance between oxidative and antioxidative systems of cells and tissues, is a result of over production of oxidative-free radicals and associated reactive oxygen species (ROS). One outcome of excessive levels of ROS is the modification of the structure and function of cellular proteins and lipids, leading to cellular dysfunction including impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity, immune activation and inflammation. Nutritional stress, such as that caused by excess high-fat and/or carbohydrate diets, promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation and decreased antioxidant status. In obesity, chronic oxidative stress and associated inflammation are the underlying factors that lead to the development of pathologies such as insulin resistance, dysregulated pathways of metabolism, diabetes and cardiovascular disease through impaired signalling and metabolism resulting in dysfunction to insulin secretion, insulin action and immune responses. However, exercise may counter excessive levels of oxidative stress and thus improve metabolic and inflammatory outcomes. In the present article, we review the cellular and molecular origins and significance of ROS production, the molecular targets and responses describing how oxidative stress affects cell function including mechanisms of insulin secretion and action, from the point of view of possible application of novel diabetic therapies based on redox regulation.

Molecular mechanisms of ROS production and oxidative stress in diabetes.

Oxidative stress is the result of the imbalance between reactive oxygen species (ROS) formation and enzymatic and nonenzymatic antioxidants. Biomarkers of oxidative stress are relevant in the evaluation of the disease status and of the health-enhancing effects of antioxidants. We aim to discuss the major methodological bias of methods used for the evaluation of oxidative stress in humans. There is a lack of consensus concerning the validation, standardization, and reproducibility of methods for the measurement of the following: (1) ROS in leukocytes and platelets by flow cytometry, (2) markers based on ROS-induced modifications of lipids, DNA, and proteins, (3) enzymatic players of redox status, and (4) total antioxidant capacity of human body fluids. It has been suggested that the bias of each method could be overcome by using indexes of oxidative stress that include more than one marker. However, the choice of the markers considered in the global index should be dictated by the aim of the study and its design, as well as by the clinical relevance in the selected subjects. In conclusion, the clinical significance of biomarkers of oxidative stress in humans must come from a critical analysis of the markers that should give an overall index of redox status in particular conditions.

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Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans

The prevalence of diabetes mellitus is rising all over the world. Uncontrolled state of hyperglycemia due to defects in insulin secretion/action leads to a variety of complications including peripheral vascular diseases, nephropathy, neuropathy, retinopathy, morbidity, and/or mortality. Large body of evidence suggests major role of reactive oxygen species/oxidative stress in development and progression of diabetic complications. In the present paper, we have discussed the recent researches on the biomarkers of oxidative stress during type 2 diabetes mellitus.

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Markers of Oxidative Stress during Diabetes Mellitus.

Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

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Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

BACKGROUND: Recent studies describe the participation of reactive oxygen and nitrogen species in hypertension. OBJECTIVE: To identify the redox imbalance in the blood of hypertensive. METHODS: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), vitamin C, transferrin, ceruloplasmin, malondialdehyde (MDA) and carbonyl group were quantified in the blood of 20 hypertensives and 21 controls. The individuals had a Body Mass Index of ≥ 18.5 and ≤ 30 kg/m(2), glycemia ≤ 100 mg/dL, serum cholesterol ≤ 200 mg/dL, and were nonsmokers, non-pregnant and non-lactating women, non-users of alopurinol and probucol, with hypertensives on antihypertensive medication. All individuals underwent a preparatory period of 4 weeks without alcohol, vitamin supplements, dexamethasone and paracetamol. RESULTS: Reduced levels of CAT (p 0.013), GSH (p 0.003) and MDA (p 0.014), and high levels of GPx (p 0.001) and ceruloplasmin (p 0.015) were obtained in the hypertensive group compared with controls. A positive correlation between systolic pressure and MDA in hypertensive and diastolic pressure and CAT in controls was obtained. CONCLUSION: The data obtained suggest that the hypertensives were in redox imbalance, despite the possibly attenuating effect of their antihypertensive medication.

Markers of redox imbalance in the blood of hypertensive patients of a community in Northeastern Brazil

Pró-antioxidantes e antioxidantes de baixo peso molecular oriundos da dieta: estrutura e função

BACKGROUND: Recent studies describe the participation of reactive oxygen and nitrogen species in hypertension. OBJECTIVE: To identify the redox imbalance in the blood of hypertensive. METHODS: Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), vitamin C, transferrin, ceruloplasmin, malondialdehyde (MDA) and carbonyl group were quantified in the blood of 20 hypertensives and 21 controls. The individuals had a Body Mass Index of > 18.5 and < 30 kg/m2, glycemia < 100 mg/dL, serum cholesterol < 200 mg/dL, and were nonsmokers, non-pregnant and non-lactating women, non-users of alopurinol and probucol, with hypertensives on antihypertensive medication. All individuals underwent a preparatory period of 4 weeks without alcohol, vitamin supplements, dexamethasone and paracetamol. RESULTS: Reduced levels of CAT (p 0.013), GSH (p 0.003) and MDA (p 0.014), and high levels of GPx (p 0.001) and ceruloplasmin (p 0.015) were obtained in the hypertensive group compared with controls. A positive correlation between systolic pressure and MDA in hypertensive and diastolic pressure and CAT in controls was obtained. CONCLUSION: The data obtained suggest that the hypertensives were in redox imbalance, despite the possibly attenuating effect of their antihypertensive medication.

Marcadores de desequilíbrio redox em sangue de pacientes hipertensos de uma comunidade no Nordeste do Brasil

Systemic Arterial Hypertension (HAS) is a condition charac- terized by endothelial dysfunction, which main role consists on stopping the vase-relaxation caused by the decreased bioactivity of the nitric oxide (NO • ) in the vascular wall, due, equally, to the oxidative stress, which represents the oxidative hypothesis of hypertension. Conceptually, the oxidative stress results in an unbalance between the antioxidant and pro-oxidant systems, making the harmful action of the reactive species of oxygen (ROS) and nitrogen prevail on the cells, tissues and vital organs. This article presents, concisely, HASendothelial oxidative stress which mainly results in the overproduction of the superoxide radical anion (O 2 • ¯), which inhibits the activity of the NOdue, mainly, to the direct reaction between these two to create peroxynitrite (ONOO¯). Peroxynitrite (ONOO¯) is a particularly harmful reactive intermediate, as it is able to generate the hydroxyl radical ( • OH) even without the presence of the transition metal. The endothelial overproduction of ROS and RNS occurs (1) through enzymatic reactions (NAD(P)H oxidase - NAD(P) Hox , xanthine oxidase - XO, lipo-oxygenase - LOx, ciclo- oxygenase - COx, and nitric oxide endothelial synthase - (eNOS)) and (2) without the participation of enzymes but through mechanical forces (shear stress of the tur- bulent blood flux and vascular stretch determined by luminal pressure).

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Hipótese oxidativa da hipertensão arterial: uma minirrevisão Oxidative hypothesis of hypertension: a mini-review

O cafe e a bebida mais consumida no Brasil e no mundo ocidental O fato de ser uma bebida tao popular, aliado a sua importância economica, explica o interesse por estudos sobre o cafe, desde a sua composicao ate seus efeitos na saude humana Dentre as diversas substâncias presentes na composicao quimica do cafe, alem dos nutrientes, destacam-se a cafeina, os diterpenos cafestol e kahweol e os acidos clorogenicos, o que faz do cafe uma importante fonte dietetica destes compostos Muitos estudos tem verificado a influencia de seus constituintes na saude, principalmente a cafeina vs a elevacao da pressao arterial; o cafestol e o kahweol vs a dislipidemia; e acidos clorogenicos vs protecao cardiovascular, por suas propriedades antioxidantes Este artigo tem como objetivo apresentar de forma sucinta a importância da bebida e sua composicao quimica, os mecanismos fisiologicos envolvidos na elevacao da pressao arterial e do colesterol serico atribuiveis ao cafe, bem como estudos selecionados que verificaram a associacao do consumo da bebida com estas doencas cardiovasculares

Sandra Mary Lima Vasconcelos

Papers

Markers of redox imbalance in the blood of hypertensive patients of a community in Northeastern Brazil

Pró-antioxidantes e antioxidantes de baixo peso molecular oriundos da dieta: estrutura e função

Marcadores de desequilíbrio redox em sangue de pacientes hipertensos de uma comunidade no Nordeste do Brasil

Hipótese oxidativa da hipertensão arterial: uma minirrevisão Oxidative hypothesis of hypertension: a mini-review

Café e saúde humana: um enfoque nas substâncias presentes na bebida relacionadas às doenças cardiovasculares