Pilar Muñiz

Antioxidant properties, radical scavenging activity and biomolecule protection capacity of flavonoid naringenin and its glycoside naringin: a comparative study

BACKGROUND This study was designed to evaluate and compare antioxidant capacity and radical scavenging activity of naringin and its aglycone by different in vitro assays. The effects of flavanones on lipid peroxidation, glutathione (GSH) oxidation and DNA cleavage were also assessed. RESULTS The results showed that naringenin exhibited higher antioxidant capacity and hydroxyl and superoxide radical scavenger efficiency than naringin. Our results evidenced that glycosylation attenuated the efficiency in inhibiting the enzyme xanthine oxidase and the aglycone could act like a more active chelator of metallic ions than the glycoside. Additionally, naringenin showed a greater effectiveness in the protection against oxidative damage to lipids in a dose-dependent manner. Both flavanones were equally effective in reducing DNA damage. However, they show no protective effect on oxidation of GSH. CONCLUSION The data obtained support the importance of characterizing the ratio naringin/naringenin in foods when they are evaluated for their health benefits.

Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community

Deletions of loci on chromosomes 5q, 17p, 18q, and 22q, together with the incidence of p53 mutations and amplification of the double minute‐2 gene were investigated in the sporadic colorectal tumors of 44 patients from a Spanish community. Chromosome deletions were analyzed by means of loss of heterozygosity analysis using a restriction fragment length polymorphism assay. Allelic losses were also detected by polymerase chain reaction (PCR)‐single‐stranded conformation polymorphism (SSCP) analysis of a polymorphic site in intron 2 of the p53 gene. The percentages of genetic deletions on the screened chromosomes were 39.3% (5q), 58.3% (17p), 40.9% (18q), and 40% (22q). Mutations in p53 exons 2–9 were examined by PCR‐SSCP analysis and direct sequencing of the mutated region. Twenty of 44 tumor samples (45.45%) showed mutations at various exons except for exons 2, 3, and 9, the most frequent changes being G → T transversion and C → T transition. Because oxygen‐free radicals play a role in the carcinogenesis process, we evaluated the oxidative status of the colorectal tumors. Antioxidant activities, lipid peroxidation, and DNA‐damaged product concentrations in colon tumors and normal mucosa were compared. In tumor tissues, superoxide dismutase and catalase decreased fourfold and twofold, respectively, whereas glutathione peroxidase and reduced glutathione increased threefold. Malondialdehyde and 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) levels were twofold higher in colorectal tumors than in normal mucosa. Seven of 10 DNA tumor samples (70%) showing higher values of 8‐OHdG also had genetic alterations at different chromosomal loci. In these samples, the p53 gene was deleted or mutated in 71.4% of cases. We concluded that the observed changes in the oxidative metabolism of the tumor cells and the consecutive increase in DNA damage may potentiate the genomic instability of different chromosomal regions, leading to further cell malignancy and tumor expansion. Mol. Carcinog. 18:232–243, 1997.

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients

ABSTRACTBackgroundTreatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting.MethodsThe study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained.ResultsBaseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased.ConclusionsIn renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

KRAS, BRAF, EGFR and HER2 gene status in a Spanish population of colorectal cancer

To evaluate the KRAS, BRAF, EGFR, and HER2 gene status in colorectal cancer by novel techniques and evaluate whether anti-HER2 therapies could be offered in the treatment of these patients. There are conflicting data on the prevalence of BRAF mutations and EGFR and HER2 gene amplification in colorectal KRAS wild type patients. In our study we tried to evaluate these expressions and their relationship to future treatment assays. Clinical–pathological data and paraffin-embedded specimens were collected from 186 patients who underwent colorectal resections at General Yagüe Hospital in Burgos, Spain. KRAS and BRAF status was analyzed by real-time PCR in all patients. EGFR and HER2/NEU gene amplification was detected using fluorescent in situ hybridisation technique (FISH) in 38 KRAS and BRAF wild type patients. KRAS mutations were present in 48% of the colorectal cancer patients. BRAF mutations were present in 6.25% of the KRAS wild type patients. EGFR and HER2 gene amplification was observed in 5.3% and 26.3%, respectively, of KRAS and BRAF wild type colorectal cancer patients. HER2, but not EGFR gene amplification, was frequently observed in KRAS and BRAF wild type colorectal cancer patients. These data indicate that HER2 amplification could be one of the genes to be considered in the therapeutic management of colorectal cancer.

Mandarin Juice Improves the Antioxidant Status of Hypercholesterolemic Children

Background: Oxidative stress has been linked to such degenerative diseases as atherosclerosis, and it has been suggested that increased dietary intake of antioxidants may reduce its progression. Objective: To determine the effect of mandarin juice consumption on biomarkers related to oxidative stress in hypercholesterolemic children. Materials and Methods: The diet of 48 children with plasma cholesterol >200 mg/dL and low-density lipoprotein cholesterol >130 mg/dL was supplemented for 28 days with 500 mL/day of pure (100%) mandarin juice (Citrus clementina Hort. ex Tan.). The composition of the mandarin juice was analyzed, and its antioxidant antiradical activity was evaluated in vitro. Malondialdehyde, carbonyl groups, vitamins E and C, erythrocyte-reduced glutathione, and plasma lipids were measured at the onset and at the end of the supplementation period. The paired Student t test was used to compare values before and after supplementation. Results: Mandarin juice exerted a strong antioxidant effect mainly due to its high hydroxyl activity and, to a lesser extent, to its superoxide scavenger activity. At the end of the study, levels of the plasma biomarkers of oxidative stress were significantly decreased (malondialdehyde −7.4%, carbonyl groups −29.1%, P < 0.01), whereas the plasma antioxidants vitamin E and C (13.5%, P < 0.001 and 68.2%, P < 0.00001, respectively) and intraerythrocyte glutathione level (36.7%, P < 0.00001) were significantly increased. Plasma lipids and antibodies to oxidized low-density lipoproteins remained unchanged. Conclusions: Regular ingestion of mandarin juice significantly reduces plasma biomarkers of lipid and protein oxidation and enhances the antioxidant status of consumers.

Influence of the Degree of Roasting on the Antioxidant Capacity and Genoprotective Effect of Instant Coffee: Contribution of the Melanoidin Fraction

The roasting process induces chemical changes in coffee beans that strongly affect the antioxidant activity of coffee. In this study, the polyphenol and melanoidin contents and the antioxidant activity of three instant coffees with different roasting degrees (light, medium, and dark) were assessed. Coffee brews were separated into fractions, and the potential biological activity of the melanoidins was evaluated by simulating their gastrointestinal digestion. Total antioxidant capacity, hydroxyl radical scavenger activity, lipid peroxidation inhibition capacity, and protection against DNA oxidative damage (in vitro and ex vivo genoprotective effects) were determined. We report that instant coffee has a high total antioxidant capacity and protective effect against certain oxidative stress biomarkers (lipids and DNA), although this capacity decreases with the roasting degree. Our study confirms the hypothesis that several of the polyphenols present in coffee may become part of the melanoidins generated during roasting. Furthermore, the elevated genoprotective effect of melanoidin-digested fractions is noteworthy.

Presence of Maillard products in Spanish muffins and evaluation of colour and antioxidant potential

Spanish muffins are bakery products widely consumed in Spain. During their elaboration process MRPs are formed, being partially responsible for muffin characteristics including their antioxidant capacity. The main aim of the study was evaluating the amount, colour and antioxidant capacity of different fractions of MRPs (low and high molecular weight) isolated from commercial muffins. The fraction of high molecular weight (melanoidins) showed to have a higher antioxidant capacity, measured by ABTS and FRAP, than LMW ones. Significant and relatively close correlations between colour parameters and antioxidant capacity were observed for global MRPs, but only occasionally when isolated fractions of melanoidins and LMW were studied. As summary, it can be said that global MRPs present in muffins, apart from contributing to colour and flavour, can also contribute significantly to muffin conservation, due to their appreciable antioxidant capacity, which seems to be directly correlated with of their colour, although this fact is not extrapolated to isolated fractions of melanoidins and LMW MRPs.

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.

Effect of a Hemodiafiltration Session with On-Line Regeneration of the Ultrafiltrate on Oxidative Stress : Comparative Study with Conventional Hemodialysis with Polysulfone

Background: The influence of a dialysis session using hemodiafiltration with on-line regeneration of the ultrafiltrate (HFR) is compared with that of a conventional hemodialysis session with polysulfone (HD-PS) and with a group of healthy individuals. Methods: Total antioxidant capacity (TAC), antioxidants, i.e., superoxide dismutase (SOD) glutathione peroxidase (GPX), reduced glutathione (GSH) and catalase, and biomarkers of oxidative stress were evaluated in plasma, whole blood and lymphocytes. Results: The study showed decreased plasma TAC, decreased activities of antioxidant enzymes and decreased GSH levels along with increased thiobarbituric-acid-reactive substances and 8–hydroxy-2-deoxyguanosine (8-OHdG) levels in lymphocytes. The antioxidants and biomarkers of lipid and protein damage after dialysis sessions with HFR were similar or better than following HD-PS. Thus, the blood GPX activity was comparable to that of healthy controls and significantly better than following HD-PS. An increase in 8-OHdG levels was observed in the HD-PS group after dialysis but not in the HFR group. Conclusions: These results show that HFR induces less oxidative stress than HD-PS.

Effect of corn oil and vitamin E on the oxidative status of adipose tissues and liver in rat

Abstract The diet is usually formed of a varying antioxidant and fatty acid content acquired from oils. The purpose of this study was to determine the effects of corn oil-rich diet supplemented or not with vitamin E on oxidative damage and antioxidant status in liver and adipose tissue of rat. Male Wistar rats were fed during 4 weeks with a hyperlipidic diet. The groups fed with hyperlipidic diets showed lower activity levels than the control groups with the exception of superoxide dismutase and glutathione peroxidase in brown adipose tissue. Supplementation of the control group with vitamin E (CE) did not produce any significant changes in the superoxide dismutase and catalase levels, but glutathione peroxidase activity increased slightly for groups supplemented with vitamin E. The hyperlipidic group supplemented with vitamin E (HE) showed a significant decrease of SOD and catalase activities in adipose tissues. Reduced glutathione levels decreased in liver from animals fed with higher quantities of corn oil. Vitamin E supplementation showed a decrease in GSH levels only for the control group (CE). Thiobarbituric acid-reactive substance (TBARS) levels were lower in the animals fed larger quantities of corn oil. Supplementation of vitamin E results in lower TBARS values.