Victoria Valls-Bellés

Oxidant mechanisms in childhood obesity: the link between inflammation and oxidative stress

Evidence of obesity-induced oxidative stress in adults has emerged in the past several years, and similar evidence has been demonstrated in children more recently. The reactive species of oxygen or nitrogen can chemically alter all major classes of biomolecules by modifying their structure and function. Organisms have developed mechanisms to protect biomolecules from the deleterious effects of free radicals. These include the enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as water and lipid-soluble antioxidants, such as glutathione, ascorbate (vitamin C), α-tocopherol (vitamin E), and β-carotene. Obesity creates oxidant conditions that favor the development of comorbid diseases. Energy imbalances lead to the storage of excess energy in adipocytes, resulting in both hypertrophy and hyperplasia. These processes are associated with abnormalities of adipocyte function, particularly mitochondrial stress and disrupted endoplasmic reticulum function. In this sense, oxidative stress can also be induced by adipocyte associated inflammatory macrophages. There is a close link among obesity, a state of chronic low-level inflammation, and oxidative stress. In addition, the dysregulation of adipocytokines, which are secreted by adipose tissue and promoted by oxidative stress, act synergistically in obesity-related metabolic abnormalities. Adipocytokines link the local and systemic inflammation responses in the context of obesity. It is thought that the evaluation of oxidative status may allow for the identification of patients at an increased risk of complications. Decreasing the levels of chronic inflammation and oxidative stress in childhood may decrease cardiovascular morbidity and mortality in adulthood.

Is obesity associated with oxidative stress in children

OBJECTIVE We evaluated the presence of oxidative stress in obese children without co-morbidities. METHODS The study population included 68 children (30 girls, 38 boys), between 6 and 14 years of age. The levels of markers of oxidative damage (malondialdehyde [MDA], and plasma carbonyl groups [CG]) and measures of antioxidant defense, such as the enzyme glutathione peroxidase (GPx) and low molecular scavengers (erythrocyte-reduced glutathione [GSH], alpha-tocopherol and beta-carotene) were determined. Children were categorized in groups by the standard deviation score of body mass index (SDS-BMI). Twenty children were non-obese (SDS-BMI< or =1.33), and the 48 obese children (SDS-BMI> or =2) were further divided into two groups: SDS-BMI> or =3 (22 children) and > or =2 SDS-BMI<3 (26 children). RESULTS The levels of MDA and CG were significantly higher (p<0.05) in children with SDS-BMI> or =3. The GPx activity was increased, while the GSH concentration was lower in obese children compared with non-obese children (p<0.01). There were no differences in serum alpha-tocopherol and beta-carotene levels between groups. MDA was the sole marker of oxidative damage that was positively correlated with SDS-BMI, (r=0.35, p=0.015), and negatively with high-density lipoprotein cholesterol (HDL-C) (r=- 0.32, p=0.027). GPx was inversely related to total cholesterol (r=- 0.34, p=0.019). In multiple regression analysis, we confirmed that SDS-BMI and HDL-C were determinants of MDA. CONCLUSIONS Severe childhood obesity is associated with oxidative stress. Thus, providing foods with high antioxidant capacity in addition to a hypocaloric diet is crucial for the treatment of obese children.

Oxidative markers in children with severe obesity following low-calorie diets supplemented with mandarin juice

Aim:  To evaluate the effect of supplementing a hypocaloric diet with mandarin juice, a food with a high content of antioxidants (vitamin C, flavonoids and carotenoids), on biomarkers of oxidant/antioxidant status of severe obese children.

α-Tocopherol, MDA-HNE and 8-OHdG levels in liver and heart mitochondria of adriamycin-treated rats fed with alcohol-free beer

Different studies indicate that oxidative stress and mitochondrial damage are key factors in different pathogenic process. The aim of this study was to investigate the possible protective role of alcohol-free beer on adriamycin-induced (ADR) heart and liver toxicity using biomarkers of oxidative stress. This effect was compared with the effect of alcohol beer intake and with a control group. Rats were randomly divided into six groups. The first group received no adriamycin, was fed with water and was regarded as the control group; the second group was injected with a ADR (two cycles of 5mg/kg); the third and fourth groups were fed with alcohol-free and beer for 21 days, respectively and the fifth and sixth groups were fed with alcohol-free and beer beginning 7 days before the administration of a first dose of ADR. Beer was administrated intragastrically and ADR (two cycles of 5mg/kg) was intraperitoneally. The levels of MDA+4HNE (malondialdehyde and 4-hydroxynonenal) in heart mitochondria was higher in the group treated with ADR alone than in the control groups, and it was lower in the groups treated with ADR that drank beer than in the ADR group alone. However, no difference was observed in liver mitochondria between the group treated with ADR and the group treated with ADR that drank beer. Significant decrease in the levels of heart and liver alpha-tocopherol was observed in the ADR group when compared to the control groups, and this decrease was normalized by beer treatment. Interestingly, the levels of antioxidant alpha-tocopherol in liver were significantly higher in rats that consumed alcohol-free beer than in those that consumed alcohol beer. Intake of alcohol-free beer showed a DNA protective effect to decreases significantly the levels of 8-OHdG levels in heart and liver increased by the ADR-treatment. In conclusion, this study clearly indicated that alcohol-free beer consumption significantly reduces the adriamycin-induced oxidative stress.

Oxidant/antioxidant status in obese children compared to pediatric patients with type 1 diabetes mellitus.

Codoñer‐Franch P, Pons‐Morales S, Boix‐García L, Valls‐Bellés V. Oxidant/antioxidant status in obese children compared to pediatric patients with type 1 diabetes mellitus.

A matter of fat: insulin resistance and oxidative stress.

Obesity is linked to insulin resistance (IR), which can lead to type 2 diabetes mellitus. Oxidative stress present in early obesity may favor the progression to comorbid conditions.

Effect of a Diet Supplemented with α-Tocopherol and β-Carotene on ATP and Antioxidant Levels after Hepatic Ischemia-Reperfusion

Ischemia-reperfusion injury associated with liver transplantation remains a serious complication in clinical practice. In the present study the effect of intake of α-tocopherol or β-carotene to limit liver injury by oxidative stress in ischemia and reperfusion was explored. Wistar rats were fed with diets enriched with α-tocopherol (20 mg/day) or β-carotene (3 mg/day) for 21 days. After 21 days, their livers were subjected to 15 and 30 min of ischemia and afterwards were reperfused for 60 min. The recovery of levels of ATP during reperfusion was better in the group of rats whose diets were supplemented with α-tocopherol or β-carotene than in the group control. The supplementation of the diet induced changes in the profile of enzymatic antioxidants. The supplementation with α-tocopherol and β-carotene resulted in a decreased of superoxide dismutase during the ischemia and a recovery was observed after reperfusion. Not changes were observed for the enzymes catalase and glutathione peroxidase and glutathione but their values were higher to those of the group control. In conclusion, the supplementation with α-tocopherol and β-carotene improve the antioxidant and energetic state of liver after ischemia and reperfusion injury.

Dried apples enriched with mandarin juice by vacuum impregnation improve antioxidant capacity and decrease inflammation in obese children.

BACKGROUND A favorable effect over development of degenerative diseases is derived of an adecuate intake of fruit and vegetables, mainly due to their antioxidant compounds OBJECTIVES The goal of this study was to test the effect in vivo over oxidant status and inflammation in obese children of a novel food product made of dried apples enriched with mandarin juice by vacuum impregnation. METHODS A four-week intervention study was conducted in 41 obese children (> 2 standard deviation score-body mass index). Participants were instructed to follow their usual diet supplemented with 40 g/day of the developed product. Anthropometric parameters were determined including body mass index, waist circumference and estimations of body fat percentage using bioelectrical impedance. Dietary intake was assessed by questionnaire. Metabolic risk factors (blood pressure, lipid profile, glucose and insulin resistance) were recorded. To determine oxidant status, plasma total antioxidant capacity and 8-hydroxydeoxyguanosine, as marker of oxidative damage to DNA, were investigated. High-sensitive C-reactive protein, tumor necrosis factor-α, and interleukins 6 and 1-α were measured as inflammatory markers. Measurements were collected at baseline and at the end of the intervention period. RESULTS Significant improvement in systolic blood pressure and lipid profile after intervention period was noted. A significant increase in the antioxidant capacity of plasma (ABTS and FRAP assays) and reductions in DNA oxidative damage and inflammatory markers were also found. CONCLUSION Overall, adding the product to the diet contributes to ameliorate oxidant and inflammatory status in obese children and several risk factors for atherosclerosis.

Dried apple enriched with mandarin juice counteracts tamoxifen-induced oxidative stress in rats.

Abstract The effect of a product made of dehydrated apples enriched with mandarin juice by vacuum impregnation on markers of oxidative stress (plasma antioxidant capacity, carbonyl groups (CGs), 8-hydroxydeoxyguanosine (8OHdG) and α-tocopherol) was tested in rats. Six groups of animals were studied: one group was fed a standard diet; two groups were supplemented with dehydrated apple either impregnated or not with mandarin juice throughout 28 days; and three groups (one unsupplemented and two supplemented) were additionally treated with tamoxifen (TAM) for 21 days used for induction of oxidative stress. The rats treated with TAM showed an increase in aminotransferases, CGs and 8OHdG. All of these effects were significantly decreased in the animals after apple snack consumption; the addition of mandarin juice into the apple mainly accounts for increased levels of α-tocopherol in plasma and liver. These findings suggest that the food product have a protective action against oxidative stress induced by TAM in rats.

Free radicals: A review

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are normally produced in aerobic organisms. Free radicals play a physiological role being necessary for cellular functioning because redox reactions are the basis for numerous biochemical pathways as well as cellular chemistry, biosynthesis of macromolecules and metabolic regulation. They can able to act as second messengers, producing the stimulation of cell proliferation and being mediators for the activation of cells. However, ROS and RNS can also lead to unwanted oxidation reactions when accumulate and if they are in high amounts they can produce toxic effects. The organism must confront and control the presence of both pro-oxidants and antioxidants continuously. The balance between these is tightly regulated and extremely important for maintaining vital cellular and biochemical functions. Although the exposure of the organism to ROS is extremely high from exogenous sources, the exposure to endogenous sources is much more important and extensive. The dual nature of these species with their beneficial and deleterious characteristics implies the complexities of their specific functioning at a biological site.