914 resultados para medicamentos


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Candida albicans is a diploid yeast that in some circumstances may cause oral or oropharyngeal infections. The investigation of natural products is mandatory for the discovery of new targets for antifungal drugs development. This study aimed to determine the genotypes of 48 clinical isolates of C. albicans obtained from the oral cavity of kidney transplant patients from two distinct geographic regions of Brazil. In addition, we investigated three virulence factors in vitro: phospholipase activity, morphogenesis and the ability to evade from polymorphonuclear neutrophils. The expression of these virulence factors in vitro was also investigated in the presence of the crude extract of Eugenia uniflora. The genotype A was the most prevalent (30 isolates; 62.5%), followed by genotype C (15 isolates; 31.5%) and genotype B (3 isolates; 6.25%). When microsatellite technique with primer M13 was applied, 80% of the isolates from the South were placed within the same cluster. All Genotype C strains were grouped together within two different clusters. Genotype C was considered more resistant to PMNs attack than genotypes A and B. Strains isolated from the South of Brazil showed higher ability to combat PMNs phagocytosis. We found a high rate of genotype C strains isolated from the oral cavity of this group of patients. The crude extract of E. uniflora inhibited proper hypha formation and phagocytosis by PMNs, but had no significant effect on phospholipase activity. This study characterized oral C. albicans strains isolated from kidney transplant recipients and will contribute for the better understanding of the pathogenesis and alternative therapeutics for oral candidiasis

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Spondias sp. (Anacardiaceae), popularly known as cajá-umbu, is an endemic plant from Northeastern Brazil, where their leaves are widely used in folk medicine to treat inflammatory processes, while their fruits have a great agro industrial potential. This study was designed to evaluate hepatoprotective, antinociceptive, antioxidant, antimicrobial and anti-inflammatory properties, as well as the acute toxicity and repeated dose 28, using a methanolic extract (MES), a fraction rich in flavonoids (FRF) and a precipitate from Spondias sp.leaves. The antioxidant activity of them was valued to evaluate their free radical scavenger capacity by DPPH test, whereas MES and FRF were used to evaluate while the preventive action on carbon tetrachloride (CCl4)-induced hepatotoxicity. Seven groups (n=5) of female Wistar rats were used as follows: control group, CCl4-intoxicated group treated with EMS (500 mg/kg) for 7 days, three CCl4-intoxicated groups treated with FRF (25, 50 and 75 mg/kg) for 7 days and the CCl4-intoxicated group treated with Legalon ® (silimarina; (phytotherapeutic reference) (50 mg/kg; 7 days). MES and FRF showed a protective action against liver injury induced by CCl4, being observed a significant reduction of serum enzyme activity marker of liver damage (alanine transaminase and aspartate transaminase). On the other hand, the lipid peroxidation (SRAT) decrease, as well as the increase of glutathione content and enzyme activity of antioxidant defense system (SOD, CAT, GPx) toward near normal values indicated the ability of EMS to restore the oxidative imbalance induced by CCl4. The histological analysis confirmed the hepatoprotection, compared to degenerative changes in CCl4-treated group. This hepatoprotetor effect was similar to that shown by Legalon®. The in vitro high antioxidant capacity of extract (93.16 ± 1.00%) showed analogous results to those obtained by Carduus marianus BHT (reference standard). This fact explains the obtained results in vivo. Although no antimicrobial activity was detected, EMS and FRF promoted the antinociceptive effect induced in the second phase by the intraplantar formalin test, evidencing the anti-inflammatory action; confirmed by the carrageenan-induced peritonitis model. The evaluation of the mechanical allodynia (CFA a 80%) demonstrated the involvement of the Spondias sp. chemical composition in the anti-inflammatory activity toward the acute processes. The acute exposure and repeated dose during 28 days did not produce significant changes in the parameters that evaluate toxicity. Together the experimental results reveal, that Spondias sp. leaf extracts have a promising potential in pharmaceutical area, and due to its non-toxic condition present efficiency and security

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Conselho Nacional de Desenvolvimento Científico e Tecnológico

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Post-menopause is a period of women s life cycle that is characterized by estrogen depletion and therefore increasing cardiovascular diseases, neurodegenerative disorders, urogenital atrophy, osteoporosis, hot flushes and sexual discomfort incidences. Estrogen is a hormone with comfirmed antioxidant action and its depletion is related to oxidative stress instalation and damaging various important biomolecules. Regular physical activity has been identified as a factor involved in reducing women s post-menopausal complications in addition to improving antioxidant defense by reducing the oxidative damage and consequently improving life s quality in this part of the population. This study aims to evaluate the influence of hypoestrogenism in antioxidant adaptation due to regular exercise, by determining reduced glutathione (GSH) and Thiobarbituric Acid Reactive Substances (SRAT) concentrations and antioxidant enzymes glutathione peroxidase (GPx), Superoxide Dismutase (SOD) and Catalase (CAT) activities in blood, brain and liver of rats. To achieve this goal we used 50 Wistar rats, weighing 180-250g which were divided into two groups, control - GC (25) and ooforectomized - GO (25). Each group was subdivided into five subgroups: Not-trained - S (5), Not-trained Acute Exercise - SEA (5), regular exercise 30 days - E30 (5), regular exercise 60 days - E60 (5) and regular exercise 90 days - E90 (5). Each of the three subgroups exercised regularly was subjected to acute exercise on the eve and the day of sacrifice to collect biological samples of blood, liver and brain and subsequent determination of SRAT concentration, GSH content and antioxidant enzymes GPx, SOD and CAT activities. The results indicated that the sedentary animals acutely exercised presented oxidative stress and regular physical activity led to antioxidant adaptation. In ooforectomized group the antioxidant adaptation seen in control animals showed to be impaired. Unlike the results from blood and liver, in brain there was a shield against oxidative damage originated by the exercise and that hypoestrogenism led to a loss of this natural antioxidant potential. Therefore, hypoestrogenism interferes negatively in antioxidant adaptation due to regular exercise

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Studies report that the pathophysiological mechanism of diabetes complications is associated with increased production of Reactive Oxygen Species (ROS)-induced by hyperglycemia and changes in the capacity the antioxidant defense system. In this sense, the aim of this study was to evaluate changes in the capacity of antioxidant defense system, by evaluating antioxidant status, gene expression and polymorphisms in the genes of GPx1, SOD1 and SOD2 in children, adolescents and young adults with type 1 diabetes. We studied 101 individuals with type 1 diabetes (T1D) and 106 normoglycemic individuals (NG) aged between 6 and 20 years. Individuals with type 1 diabetes were evaluated as a whole group and subdivided according to glycemic control in DM1G good glycemic control and DM1P poor glycemic control. Glycemic and metabolic control was evaluate by serum glucose, glycated hemoglobin, triglycerides, total cholesterol and fractions (HDL and LDL). Renal function was assessed by measurement of serum urea and creatinine and albumin-to-creatinine ratio (ACR) in spot urine. Antioxidant status was evaluate by content of reduced glutathione (GSH) in whole blood and the activity of erythrocyte enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD). We also analyzed gene expression and gene polymorphisms of GPx1 (rs1050450), SOD1 (rs17881135) and SOD2 (rs4880) by the technique of real-time PCR (Taqman®). Most individuals with DM1 (70.3%) had poor glycemic control (glycated hemoglobin> 8%). Regarding the lipid profile, individuals with type 1 diabetes had significantly elevated total cholesterol (p <0.001) and LDL (p <0.000) compared to NG; for triglycerides only DM1NC group showed significant increase compared to NG. There was an increase in serum urea and RAC of individuals with DM1 compared to NG. Nine individuals with type 1 diabetes showed microalbuminuria (ACR> 30 mg / mg). There was a decrease in GSH content (p = 0.006) and increased erythrocyte GPx activity (p <0.001) and SOD (p <0.001) in DM1 group compared to NG. There was no significant difference in the expression of GPx1 (p = 0.305), SOD1 (.365) and SOD2 (0.385) between NG and DM1. The allele and genotype frequencies of the polymorphisms studied showed no statistically significant difference between the groups DM1 and NG. However, the GPx1 polymorphism showed the influence of erythrocyte enzyme activity. There was a decrease in GPx activity in individuals with type 1 diabetes who had a polymorphic variant T (p = 0.012). DM1 patients with the polymorphic variant G (AG + GG) for polymorphism of SOD2 (rs4880) showed an increase in the RAC (p <0.05). The combined data suggest that glucose control seems to be the predominant factor for the emergence of changes in lipid profile, renal function and antioxidant system, but the presence of the polymorphisms studied may partly contribute to the onset of complications

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The frequency of disseminated candidiasis caused by yeast has enhancing in intensive care unit. Despite the availability of new antifungal drugs, C. albicans sepsis mortality causes can be as high as 30-40%. So, it has been needed to looking for a new therapeutic medicament that helps in treatment and prevention of this infection. Previous data that demonstrated that particulated β-glucan stimulates the immune system and experiments of this work were conducted to investigating if β-glucan extracted from Saccharomices cerevisiae, could modified the evolution of mouse model C. albicans systemic infection. Balb/c mice with sepsis and β-1,3 glucan treated or not were analyzed the influence of β-1,3 glucan in survival of the animals, in the fungal burdens in kidney, in the production of urea and TNF even in the histopathology of kidney. The experiments shown that the infected animals a nd glucan treated had great survival (p<0,05), less unit form colony in kidney and normal levels of urea. In the kidney histopathology of not glucan treated animals it has seen more lesions when compared with treated animals. So we conclude that β-1,3 glucan could stimulate the immune system against disseminated C. albicans

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Retinoic acid (RA) and hydroquinone (HQ) assets are widely used in pharmaceutical and cosmetic formulations, for having depigmenting properties and are largely produced in drugstores. To assist in the development of formulations containing the active RA and HQ National Forms of Brazilian Pharmacopoeia (2005 and 2012 ) proposes formulations with different excipients such as cetyl alcohol (AC), cetostearyl alcohol (ACT), methylparaben (MTP), propyl paraben ( PPB), glycerin (GLY), dipropylene glycol (DPG), imidazolidinil urea ( IMD ), cyclomethicone (CCM ), butylated hydroxytoluene (BHT), octyl stearate (ETO), EDTA, decil oleate (ODC) and hydroxipropymethyl celullose (HPMC). One of the difficulties found in most cosmetic formulations is the large number of incompatibilities between the components of the formulations, so the aim this study was to evaluate thermal stability and interactions between these active pharmaceutical ingredients and excipients. The depigmenting agents were analyzed by DSC and TG and excipients were analyzed by TG. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-900 ºC, under an atmosphere of nitrogen at 50 mL min-1. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10ºC min-1, in the temperature range of 25-400ºC. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study no were found interactions between AR and the following excipients: MTP, PPB, IMD, ODC, EDTA, CCM, ETO, HPMC. However, were found interactions with the following excipients: AC, ACT, BHT, GLI and DPG. For HQ were found interactions with IMD and DPG. Interactions remained even changing proportions of the mixtures and the ternary. Thus, the studies conducted with excipients of National Formulary from 2005 and 2012 showed that these new excipients do not interact by thermogravimetry with the active pharmaceutical ingredients of this study

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Since its synthesis over 48 years rifampicin has been extensively studied. The literature reports the characterization of thermal events for rifampicin in nitrogen atmosphere, however, no characterization in synthetic air atmosphere. This paper aims to contribute to the thermal study of rifampicin through thermal (TG / DTG, DTA, DSC and DSC - FOTOVISUAL ) and non-thermal (HPLC, XRPD , IR - FTIR , PCA) and its main degradation products ( rifampicin quinone , rifampicin N-oxide 3- formylrifamicin). Rifampicin study was characterized as polymorph form II from techniques DSC, IR and XRPD. TG curves for rifampicin in synthetic air atmosphere showed higher thermal stability than those in N2, when analyzed Ti and Ea. There was characterized as overlapping events melting and recrystallization under N2 with weight loss in the TG curve, suggesting concomitant decomposition. Images DSCFotovisual showed no fusion event and showed darkening of the sample during analysis. The DTA curve in synthetic air atmosphere was visually different from DTA and DSC curves under N2, suggesting the absence of recrystallization and melting or presence only decomposition. The IV - FTIR analysis along with PCA analysis and HPLC and thermal data suggest that rifampicin for their fusion is concomitant decomposition of the sample in N2 and fusion events and recrystallization do not occur in synthetic air atmosphere. Decomposition products studied in an air atmosphere showed no melting event and presented simultaneously to the decomposition initiation of heating after process loss of water and / or solvent, varying the Ti initiating events. The Coats - Redfern , Madsudhanan , Van Krevelen and Herwitz - Mertzger kinetic parameters for samples , through the methods of OZAWA , in an atmosphere of synthetic air and / or N2 rifampicin proved more stable than its degradation products . The kinetic data showed good correlation between the different models employed. In this way we contribute to obtaining information that may assist studies of pharmaceutical compatibility and stability of substances

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The synthetic guanylhydrazones WE010 (3,5-di-tert-butil-4-hidroxibenzaldehyde-guanylhydrazone), WE014 (4-bifenilcarboxialdehydeguanylhydrazone) and WE017 (3,4-diclorobenzaldehydeguanylhydrazone) showed high cytotoxic activity in terms of percentage inhibition of cancer cells growth. However, further progress in the development of these drug candidates requires precise and convenient methods for their qualitative and quantitative analyses. The aim of this study was to develop and validate High Performance Liquid Chromatography with diode-array detection (HPLC-DAD) and Ultra Fast Liquid Chromatography with diode-array detection (UFLC-DAD) methods suitable for as simultaneous as isolated determination of studied guanylhydrazones, based on the optimization of chromatographic parameters and obtaining reduced detection times. The chromatographic analyses of analytes by HPLC were performed on C18 ACE analytical column (150 mm x 4.6 mm), with a particle size of 5.0 μm. Among all the conditions assayed, the best results of separation were obtained with a mixture of methanol:water (60:40, v/v) as the mobile phase at a flow rate 1.5mL/min and pH of 3.5 adjusted at acetic acid. The UFLC method was developed by experimetal desing techniques in order to find optimal chromatographic analytical conditions, which were achieved on XR-ODS analytical column (50 mm x 3.0 mm), with a particle size of 2,2 μm, maintained at 25 ºC. The mobile phase was consisted of methanol:water (65:35, v/v) with 0.1% triethylamine (TEA) and pH of 3.5 adjusted at acetic acid, at a flow rate 0.5 mL/min. The procedure were validated following evaluating parameters such as specificity, linearity, limits of detection (LD) and quantification (LQ), precision, accuracy and robustness, giving results within the acceptable range. Although the UFLC method shows better sensitivity (lower values of LD and LQ), robustness (lower rates of relative standard deviation) and minimize spending time and solvent, both developed methods were adequately applied to the analysis of guanylhydrazones molecules, may be used in routine of quality control laboratories. Keywords: guanylhydrazones, HPLC/DAD, UFLC/DAD, validation of analitical method

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New drug delivery systems have been used to increase chemotherapy efficacy due the possible drug resistance of cancer cells. Poly (lactic acid) (PLA) microparticles are able to reduce toxicity and prolong methotrexate (MTX) release. In addition, the use of PLA/poloxamer polymer blends can improve drug release due to changes in the interaction of particles with biological surfaces. The aim of this study was developing spray dried biodegradable MTX-loaded microparticles and evaluate PLA interactions with different kinds of Pluronic® (PLUF127 and PLUF68) in order to modulate drug release. The variables included different drug:polymer (1:10, 1:4.5, 1:3) and polymer:copolymer ratios (25:75, 50:50, 75:25). The precision and accuracy of spray drying method was confirmed assessing drug loading into particles (75.0- 101.3%). The MTX/PLA microparticles showed spherical shape with an apparently smooth surface, which was dependent on the PLU ratio used into blends particles. XRD and thermal analysis demonstrated that the drug was homogeneously dispersed into polymer matrix, whereas the miscibility among components was dependent on the used polymer:copolymer ratio. No new drug- polymer bond was identified by FTIR analysis. The in vitro performance of MTX-loaded PLA microparticles demonstrated an extended-release profile fitted using Korsmeyer- Peppas kinetic model. The PLU accelerated drug release rate possible due PLU leached in the matrix. Nevertheless, drug release studies carried out in cell culture demonstrated the ability of PLU modulating drug release from blend microparticles. This effect was confirmed by cytotoxicity observed according to the amount of drug released as a function of time. Thus, studied PLU was able to improve the performance of spray dried MTX-loaded PLA microparticles, which can be successfully used as carries for modulated drug delivery with potential in vivo application

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Spondias mombin is a fruitful species dispersed in tropical regions of America, Africa and Asia. In Brazil, the species can be found mainly in the northern and northeastern regions. Scarce chemical and pharmacological studies have been reported for S. mombin and until this moment studies about chemical markers were not developed. In this context, the aims of this study were to characterize the chemical markers from S. mombin leaves and evaluate their anti-inflammatory, antioxidant and antiproliferative potentials. The chemical profile of the hydroethanolic extract from S. mombin leaves analyzed by HPLC-DAD, through a validated method, allowed the identification and quantification of ellagic acid and chlorogenic acid. This extract showed anti-inflammatory potential in acute peritonitis model induced by carrageenan. The hydroethanolic extract from S. mombin leaves was subjected to a liquid-liquid partition with the solvents: n-hexane, dichloromethane, ethyl acetate and n-butanol. Regarding the anti-inflammatory potential of the fractions obtained they were active; however, ethyl acetate fraction at 200 mg/kg showed highlighted results. The compounds ellagic acid and chlorogenic acid also inhibited the leukocyte migration to the site of inflammation at 2.5, 5 and 10 mg/kg. The hydroethanolic extract, fractions and the chemical markers showed significant antioxidant potential when evaluated in different assays: DPPH Free-Radical Scavenging, Superoxide Radical Scavenging, Hydroxyl Radicals Scavenging and Reducing Power. Taken together our results showed that hydroethanolic extract of S. mombin leaves has ellagic acid and chlorogenic acid as bioactive markers and it demonstrated antiinflammatory and antioxidant properties besides no cytotoxicity against 3T3 cells. It enables us to suggest S. mombin as an important species to develop herbal drugs

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Licania rigida Benth., Licania tomentosa (Benth.) Fritsch, and Couepia impressa Prance (Chrysobalanaceae family) plants have long been used medicinally by the people from Northeastern Brazil. Crude extracts and infusions of these plants have been applied in the treatment of several conditions such as diabetes and rheumatism, degenerative diseases with involvement of reactive oxygen species (ROS). The aim of this study was to evaluate the aqueous, ethanolic, and hydroethanolic leaves extracts antioxidant capacity of these species, using several in vitro assay systems (reducing power, DPPH● scavenging, the β-carotene linoleate model system and lipid peroxidation inhibition in rat brain homogenate, using thiobarbituric acid reactive substances - TBARS). The oral acute toxicity of aqueous extracts was also evaluated in vivo. Results revealed that these extracts possess a potent reducing power and DPPH scavenging ability, as well as the ability to prevent TBARS formation in rat brain homogenate in a concentration-dependent manner. Regarding in vivo oral acute toxicity of the aqueous species extracts, no toxic effects were observed upon evaluating physiological, hematological and biochemical parameters. The presence of high levels of phenolics and flavonoids was determined mainly in the ethanol extract. However, the C. impressa hydroethanolic extract, fractionated with hexane, chloroform and ethyl acetate for analysis by NMR 1H, showed more efficient results than the reference antioxidant Carduus marianus. The classes of organics compounds were determined were phenolics in the fraction of ethyl acetate and terpenes in chloroform and hexane fractions. The ethil acetate fraction had the highest content of flavonoids and increased scavenging capacity of DPPH●, possibly by the presence of phenolic compounds. Therefore, a detailed investigation of the phytochemical composition and in vivo study of the C. impressa hydroethanolic extract is suggested to characterize the active compounds of the species

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Hormone therapy is an important tool in the treatment of breast cancer and tamoxifen represents one of the most important drugs used in this type of treatment. Recently other drugs based on the inhibition of aromatase had been developed, this enzyme is responsible for the synthesis of estrogenic esteroids from the androgenic ones. The objective of this study would be the development of a quantitative cytological model of murine estral analysis that allowed the characterization of different hormone drugs effect over vaginal epithelium. The technique of monochromatic staining with Evans blue (C.I. 23860) showed to be efficient in the qualitative and quantitative classification of the cycle. It had been observed differences in the cytological standard of animals submitted to the studied drugs; tamoxifen presented a widening of phases of lesser maturation (diestrais), while anastrozole and exemestane increased the duration of the phases of larger maturation (estrais). The data were analysed through a cubical non linear regression (spline) which allowed a better characterization of the drugs, suggesting a proper cytological profile to the antagonism of the estrogen receptor (tamoxifen), aromatase competition (anastrozole) and inhibition of the enzyme (exemestane)

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This qualitative research aimed to understand the educational activities carried out in Family Health Units, of the municipality of Mossoró-RN. It was used symbolic cartography to organize and present data from reality. It started on the approach of Health Education and knowledge transformation practice, aiming at the development of autonomy and responsibility of individuals and healthcare, publicized by the appreciation of the interpersonal relations area established in services, such as educational emancipator practices contexts. Individual and collective interviews were realized, conducted with health professionals and users of ESF, about themes, activities, membership, the difficulties, the potential and the design of health education that permeate everyday Family Health Strategy. From what was apprehended, thematic maps were done with the analysis of educational practices of professionals belonging to the Family‟s Health. Links are built with the wires of conceptions of education reflected on themes and activities of family health teams. The storylines are rebinded by voices about the difficulties and the potential of educational processes for emancipator postures. For users, health education means proper care and information on disease prevention. Professionals understand that it is all information that is given to users, about health, social well-being, economic and general condition of human being as a way of preventing and treating disease. Mark printed on voices denote that activities and themes worked don‟t motivate users enough for their participation, being that physicians and dentists also get excluded themselves from educational practices. Elderly groups are those who get most involved with the activities. The size of the contained area and its seclusion from community make harder the access of users, as well as diminishing the quality of educational actions and links users-professionals. Therefore, the searching for medicines, medical consultations and wish to be well served are trademarks of voices from the users that interconnect with enlightening information and guidelines offered by professionals to users. It brings out practices that need to incorporate the social, the subjective and act with practices of prevention and health promotion, on the basis of lifestyles. The dialogical model, which needs to be approached since planning phase of health education actions could arouse interest of involved groups; promoting a relationship of dialogue and listening; discussing the local reality; stimulating practical methodological dialetics; promoting processes of deconstruction of concepts, values and attitudes, as more necessary than construction, using multiple languages. The defended thesis denotes paths to other studies aimed at understanding a dialogical template committed to exchanges of knowledge, and discover strategies that encourage formation of critical consciousness and the discovery of how is the training of new generations of healthcare professionals to belong to the project of society, in its technical, scientific, pedagogical, ethical, political and humanistic dimensions

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Alpha-lipoic acid (ALA) is a potent antioxidant with favourable anti-inflammatory, metabolic and endothelial effects, and has been widely investigated due to its potential against cardiovascular risk factors. This study aimed to evaluate the effect of oral ALA supplementation on oxidative stress biomarkers, inflammation and cardiovascular risk factors in patients with hypertension. This is a double-blind placebo-controlled randomized clinical trial, where the intervention was evaluated prospectively comparing results in both groups. The sample consisted of 64 hypertensive patients who were randomly distributed into ALA group (n = 32), receiving 600 mg / day ALA for twelve weeks and control group (n = 32), receiving placebo for the same period. The following parameters were evaluated before and after intervention: lipid peroxidation, content of reduced glutathione (GSH), enzymatic activities of glutathione peroxidase (GPx) and superoxide dismustase, ultrasensitive C-reactive protein (hs-CRP), triglycerides, total cholesterol and fractions, fasting glucose and anthropometric indicators. There was a statistically significant reduction (p <0.05) in serum concentrations of total cholesterol, very low density lipoprotein (VLDL), high density lipoprotein (HDL), triglycerides and blood glucose. There was a reduction in body weight and waist, abdominal and hip circumferences in the group that received ALA. In addition, there was a statistically significant increase (p <0.05) in the contents of reduced glutathione (GSH) and glutathione peroxidase (GPx) in the group receiving ALA. Oral administration of ALA appears to be a valuable adjuvant therapy, which may contribute to decrease the damage caused by oxidative stress and other risk factors associated with the atherosclerotic process