Correlación entre el grado de hipertensión arterial y el índice de estrés oxidativo. Estudio de cohorte en una población de pacientes hipertensos sistémicos en República Dominicana / Correlation between the arterial hypertension degree and oxidative stress index. Cohort study in a population of systemic hypertensive patients in Dominican Republic

Introducción: la hipertensión arterial (HTA) es una de las mayores cargas de enfermedad y riesgo para infarto cardíaco, la insuficiencia cardíaca y el fallo renal. Se reconoce que el estrés oxidativo (EO) es un determinante en el desarrollo de complicaciones y el progreso de la HTA. Se determinó el índice de EO (IEO) en individuos con HTA y en un grupo sano control, para evaluar su posible correlación. Materiales y métodos: se midió IEO en una población de 112 individuos con HTA de distintos grados entre 50 y 70 años escogidos al azar y se comparó con los valores de un grupo control de voluntarios sanos, con la intención de definir el grado de correlación entre los niveles del IEO y la severidad de HTA, mediante la medición de biomarcadores para el EO en lisado de eritrocitos. Resultados: a pesar de que los beneficios de la terapia antioxidante (TAO) no han sido definitivamente probadas, en gran parte porque las enfermedades complejas no dependen de un solo componente fisiopatogénico, el EO sigue siendo una piedra angular en el desarrollo de complicaciones y el empeoramiento de los cuadros clínicos de muchos padecimientos. La demostración de biomarcardores específicos mejora la posibilidad de una TAO dirigida. El presente ensayo demostró que la edad, el género y la etnia no influyen en el IEO y que el EO fue severo en los casos de HTA iii, moderado en HTA ii y estuvo ausente en el subgrupo con HTA grado i. Conclusiones: estos resultados sugieren una relación entre los niveles de EO y severidad de HTA y sustenta evidencias para diseñar nuevos ensayos clínicos que evalúen la eficacia de una TAO adyuvante en el manejo de la HTA

Introduction: Arterial hypertension (AHT) is one of the major burdens of disease and risk for cardiac infarction, heart failure and renal failure. It is recognized that the oxidative stress (OS) is a determining factor in the development of complications and the progress of the AHT. OS Index (OSI) in individuals with AHT and a healthy control group, was determined to assess their possible correlation. Methods: OSI was measured in a population of 112 individuals with AHT of different levels between 50 and 70 years old, chosen at random and compared with the values of healthy volunteers control group with the aim of defining the degree of correlation between the levels of the OSI and the AHT severity, by measuring biomarkers for OS in a red cell lysate. Discussion: Despite the benefits of an antioxidant therapy (AOT) have not been definitely proven, largely because the complex diseases do not depend on a single pathophysiological component, OS remains as a cornerstone in the development of complications and the worsening of the clinical pictures of many ailments. The demonstration of specific biomarkers improve the possibility of an addressed AOT. This trial showed th at the age, gender and ethnicity do not influence the OSI and that OS was severe in HTA iii cases, moderate in HTA ii cases and was absent in the subgroup with HTA i. Conclusions: These results suggest a relationship between levels of EO and severity of hypertension and support evidence to design new clinical trials assessing the efficacy of an adjuvant AOT in the management of HTA

Lack of in vivo embryotoxic and genotoxic activities of orally administered stem bark aqueous extract of Mangifera indica L. (Vimang).

Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a new natural product with antioxidant, anti-inflammatory and immunomodulatory effects known by the brand name of its formulations as Vimang. Previously, the oral toxicity studies of the extract showed a low toxicity potential up to 2000 mg/kg. This work reports the results about teratogenic and genotoxicologic studies of MSBE. For embryotoxicity study, MSBE (20, 200, or 2000 mg/kg/day) was given to Sprague-Dawley rats by gavage on days 6-15 of gestation. For genotoxicity, MSBE was administered three times during 48 h to NMRI mice. Cyclophosphamide (50 mg/kg) was used as a positive control. No maternal or developmental toxicities were observed when the rats were killed on day 20th. The maternal body-weight gain was not affected. No dose-related effects were observed in implantations, fetal viability or external fetal development. Skeletal and visceral development was similar among fetuses from all groups. No genotoxicity was observed in bone marrow erythrocytes and liver cells after administration. MSBE appears to be neither embryotoxic nor genotoxic as measured by bone marrow cytogenetics in rodents.

Effect of Mangifera indica L. extract (QF808) on protein and hepatic microsome peroxidation.

The antioxidant activities of QF808, a steam bark extract of Mangifera indica L., were studied on hydroxyl-mediated oxidation of bovine serum albumin (BSA) and in a hepatic microsome system. The extract was effective in reducing the oxidation of BSA, since its half- maximal inhibition concentration (IC(50)) was 0.0049% w/v in the inhibition of carbonyl group formation and lower than 0.0025% w/v in the inhibition of sulfhydryl group loss. QF808 inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate (NADPH), IC(50)= 0.00075% w/v, or non-enzymatically by ascorbic acid, IC(50) = 0.0126% w/v. The extract tested did not inhibit NADPH-dependent cytochrome P-450 reductase activity, since it had no effect on the oxidation rate of NADPH. These results suggest that QF808 has an antioxidant activity, probably due to its ability to scavenge free radicals involved in microsome lipid peroxidation. In addition, QF808 antioxidant profile in vitro is probably similar to its principal polyphenolic component, mangiferin, a glycosylated xanthone.

Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang).

Vimang is an aqueous extract of Mangifera indica used in Cuba to improve the quality of life in patients suffering from elevated stress. To assess its possible analgesic and antiinflammatory effects, the results of a standard extract evaluation are presented. Analgesia was determined using acetic acid-induced abdominal constriction and formalin-induced licking. Antiinflammatory effects were evaluated using carrageenan- and formalin-induced oedema. Vimang (50-1000 mg/kg, p.o.) exhibited a potent and dose-dependent antinociceptive effect against acetic acid test in mice. The mean potency (DE(50)) was 54.5 mg/kg and the maximal inhibition attained was 94.4%. Vimang (20-1000 mg/kg, p.o.) dose-dependently inhibited the second phase of formalin-induced pain but not the first phase. The DE(50) of the second phase was 8.4 mg/kg and the maximal inhibition was 99.5%, being more potent than indomethacin at doses of 20 mg/kg. Vimang (20-1000 mg/kg, p.o.) significantly inhibited oedema formation (p < 0.01 or p < 0.05) of both carrageenan- and formalin-induced oedema in rat, guinea-pigs and mice (maximal inhibitions: 39.5, 45.0 and 48.6, respectively). The inhibitions were similar to those produced by indomethacin and sodium naproxen, p.o. The different polyphenols found in Vimang could account for the antinociceptive and antiinflammatory actions reported here for the first time for M. indica bark aqueous extract.

"Mangifera indica L. extract (QF808) reduces ischaemia-induced neuronal loss and oxidative damage in the gerbil brain".

The effect of oral administration of Mangifera indica L. extract (QF808) on ischemia-reperfusion-induced neuronal death in the gerbil hippocampal CA1 sector was examined. Oral administration of QF808 for 7 days dose-dependently protected against neuronal cell death following transient ischaemia and reperfusion as assessed by histopathology. In addition, locomotor activity assessment prior to ischaemia and 7 days after correlated well with the histological results. To evaluate redox alterations by reactive oxygen species, total sulfhydryl, non-protein sulfhydryl groups (NPSH), malondialdehyde + 4-hydroxyalkenals and total nitrogen oxide levels were assayed in hippocampus and cortex homogenates. QF808 treatment attenuated NPSH loss, nitrogen oxide levels and lipid peroxidation in the hippocampus. These results suggest that orally administered QF808 is absorbed across the blood-brain barrier and attenuates neuronal death of the hippocampal CA1 area after ischaemia-reperfusion. These protective effects are most likely due to the antioxidant activity of QF808.

Protective effects of Mangifera indica L. extract, mangiferin and selected antioxidants against TPA-induced biomolecules oxidation and peritoneal macrophage activation in mice.

We compared the protective abilities of Mangifera indica L. stem bark extract (Vimang) 50-250 mgkg(-1), mangiferin 50 mgkg(-1), vitamin C 100 mgkg(-1), vitamin E 100 mgkg(-1)and beta -carotene 50 mgkg(-1)against the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative damage in serum, liver, brain as well as in the hyper-production of reactive oxygen species (ROS) by peritoneal macrophages. The treatment of mice with Vimang, vitamin E and mangiferin reduced the TPA-induced production of ROS by the peritoneal macrophages by 70, 17 and 44%, respectively. Similarly, the H(2)O(2)levels were reduced by 55-73, 37 and 40%, respectively, when compared to the control group. The TPA-induced sulfhydryl group loss in liver homogenates was attenuated by all the tested antioxidants. Vimang, mangiferin, vitamin C plus E and beta -carotene decreased TPA-induced DNA fragmentation by 46-52, 35, 42 and 17%, respectively, in hepatic tissues, and by 29-34, 22, 41 and 17%, in brain tissues. Similar results were observed in respect to lipid peroxidation in serum, in hepatic mitochondria and microsomes, and in brain homogenate supernatants. Vimang exhibited a dose-dependent inhibition of TPA-induced biomolecule oxidation and of H(2)O(2)production by peritoneal macrophages. Even if Vimang, as well as other antioxidants, provided significant protection against TPA-induced oxidative damage, the former lead to better protection when compared with the other antioxidants at the used doses. Furthermore, the results indicated that Vimang is bioavailable for some vital target organs, including liver and brain tissues, peritoneal exudate cells and serum. Therefore, we conclude that Vimang could be useful to prevent the production of ROS and the oxidative tissue damages in vivo.

Evaluation of the in vitro antioxidant activity of Mangifera indica L. extract (Vimang).

An extract of Mangifera indica L. (Vimang) was tested in vitro for its antioxidant activity using commonly accepted assays. It showed a powerful scavenger activity of hydroxyl radicals and hypochlorous acid and acted as an iron chelator. The extract also showed a significant inhibitory effect on the peroxidation of rat-brain phospholipid and inhibited DNA damage by bleomycin or copper-phenanthroline systems.