Sucralose causes non-selective CD4 and CD8 lymphotoxicity via probable regulation of the MAPK8/APTX/EID1 genes: An in vitro/in silico study.

One of the most widely used sweeteners in the world is sucralose. With sweetening power 600 times greater than sucrose, its use grows among those who seek to cut calories. Research shows that when heated, sucralose generates toxic products that attack the organism and interact with DNA. Our objective was to test this sweetener under unheated conditions and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+ , CD4+ , and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. Our results showed that sucralose reduces non-selectively the total lymphocytes due to falls in the levels of the CD4+ , CD8+ , and CD4+ CD8+ subpopulations. We observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that sucralose modulates the gene expression, interfering especially with the MAPK8, APTX, and EID1 genes. This article presents the results of an evidence-based approach to the safety of human health in the use of sucralose. Finally, this study points out that sucralose has cytotoxic, genotoxic, and mutagenic effects in the concentrations and conditions tested in human lymphocyte cell culture.

Steviol, the active principle of the stevia sweetener, causes a reduction of the cells of the immunological system even consumed in low concentrations.

AIM: Steviol is a natural diterpenoid glycoside isolated from Stevia rebaudiana Bertoni leaves and widely used as a non-caloric sweetener. In addition to their sweet taste, Steviol glycosides may also have some therapeutic benefits. There are few reports on the cytotoxicity of Steviol in human cells. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. METHODS: For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+, CD4+, and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. RESULTS AND CONCLUSION: Our results showed that Steviol reduces the number of lymphocytes due to falls of CD4+, CD8+, and CD4+CD8+ subpopulations. Besides, we observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that Steviol modulates gene expression, mainly interfering with the SESN1, NAP1L1, SOX4, and TREX1 genes. Although Steviol is used globally as a sweetener, its use should be cautious, as our study points out that Steviol has cytotoxic, genotoxic and mutagenic effects in the concentrations and conditions tested in the culture of human lymphocyte cells.

Design, synthesis, and evaluation of novel 2-substituted 1,4-benzenediol library as antimicrobial agents against clinically relevant pathogens.

Development of new antimicrobial agents, capable of combating resistant and multidrug-resistant fungal and bacterial clinical strains, is necessary. This study presents the synthesis and antimicrobial screening of 42 2-substituted-1,4-benzenediols, being 10 novel compounds. In total, 23 compounds showed activity against fungi and/or bacteria. Benzenediol compounds 2, 5, 6, 8, 11, and 12 demonstrated broad spectrum antimicrobial actions, including resistant and multidrug-resistant species of dermatophytes (Trichophyton mentagrophytes), Candida spp. and the ESKAPE panel of bacteria. Minimum inhibitory concentrations of these compounds for fungi and bacterial strains ranged from 25 to 50 µg/ml and 8-128 µg/ml, respectively. The antifungal mechanism of action is related to the fungal cell wall of dermatophytes and membrane disruption to dermatophytes and yeasts, in the presence of compound 8. Specific structural changes, such as widespread thinning along the hyphae and yeast lysis, were observed by scanning electron microscopy. The effects of compound 8 on cell viability are dose-dependent; however they did not cause genotoxicity and mutagenicity in human leukocyte cells nor haemolysis. Moreover, the compounds were identified as nonirritant by the ex-vivo Hen's egg test-chorioallantoic membrane (HET-CAM). The furan-1,4-benzenediol compound 5 showed in vivo efficacy to combat S. aureus infection using embryonated chicken eggs. Therefore, the compounds 8, and 5 are promising as hits for the development of new antimicrobial drugs with reduced toxicity.

Evaluation of genotoxic and cytotoxic effects of hydroalcoholic extract of Euphorbia tirucalli (Euphorbiaceae) in cell cultures of human leukocytes.

Euphorbia tirucalli (L.), commonly known as aveloz, has been indiscriminately used in popular medicine to treat various illnesses. However, some components can have devastating consequences. Injury to a cell's genetic material can cause mutations, cancer, and cell death. Our main goal in this work was to evaluate the genotoxic and cytotoxic effects of E. tirucalli extract on human leukocytes. For this purpose, we performed a phytochemical analysis to evaluate the plant's components. In the second step, we treated cultured human leukocytes with different concentrations of the dry extract of the plant and then evaluated the oxidative and genotoxic profiles of these leukocytes. We found that at 1% and 10% concentrations, the aveloz extract acted as a genotoxic agent that could damage DNA and increase oxidative damage. We conclude that despite its popular use, aveloz can act as a genotoxic agent, especially when it contains phorbol ester. Aveloz's indiscriminate use might actually promote tumors and therefore carry a considerable genetic risk for its users.

In vitro and in silico toxicity evaluation of bioactive 4'-aminochalcone derivatives.

The 4'-aminochalcones compounds are open-chain flavonoids structures which have shown a known array of pharmacological activities, such as antibacterial, antifungal, anti-inflammatory and antitumor effects. There is little toxicological information available about these compounds in the literature. Therefore, the investigation of toxic effects of three 4'-aminochalcone derivatives was performed using in silico and in vitro assays. In silico provided results that indicated the occurrence of mutagenic and genotoxic effects. In vitro tests, using Cellular Proliferation and Viability, Micronucleus, and DNA damage by Comet assay, showed that the compounds studied also present mutagenic and genotoxic effects, which confirm the result determined by the in silico analysis. The use of experimental and computational models is complementary to each other and the results determined for 4'-aminochalones suggest that the chalcones should also be carefully considered since they show some risks to cause toxic effects to human cells.

GBR 12909 administration as an animal model of bipolar mania: time course of behavioral, brain oxidative alterations and effect of mood stabilizing drugs.

Polymorphisms in the human dopamine transporter (DAT) are associated with bipolar endophenotype. Based on this, the acute inhibition of DAT using GBR12909 causes behavioral alterations that are prevented by valproate (VAL), being related to a mania-like model. Herein our first aim was to analyze behavioral and brain oxidative alterations during a 24 h period post-GBR12909 to better characterize this model. Our second aim was to determine the preventive effects of lithium (Li) or VAL 2 h post-GBR12909. For this, adult male mice received GBR12909 or saline being evaluated at 2, 4, 8, 12 or 24 h post-administration. Hyperlocomotion, levels of reduced glutathione (GSH) and lipid peroxidation in brain areas were assessed at all these time-points. GBR12909 caused hyperlocomotion at 2 and 24 h. Rearing behavior increased only at 2 h. GSH levels decreased in the hippocampus and striatum at the time points of 2, 4, 8 and 12 h. Increased lipid peroxidation was detected at the time-points of 2 and 12 h in all brain areas studied. At the time-point of 2 h post-GBR12909 Li prevented the hyperlocomotion and rearing alterations, while VAL prevented only rearing alterations. Both drugs prevented pro-oxidative changes. In conclusion, we observed that the main behavioral and oxidative alterations took place at the time-period of 2 h post-GBR12909, what points to this time-period as the best for the assessment of alterations in this model. Furthermore, the present study expands the predictive validity of the model by the determination of the preventive effects of Li.

Preclinical Evidences for an Antimanic Effect of Carvedilol.

Oxidative imbalance, alterations in brain-derived neurotrophic factor (BDNF), and mitochondrial dysfunction are implicated in bipolar disorder (BD) pathophysiology and comorbidities, for example, cardiovascular conditions. Carvedilol (CVD), a nonselective beta-blocker widely used for the treatment of hypertension, presents antioxidant and mitochondrial stabilizing properties. Thus, we hypothesized that CVD would prevent and/or reverse mania-like behavioral and neurochemical alterations induced by lisdexamfetamine dimesylate (LDX). To do this, male Wistar rats were submitted to two different protocols, namely, prevention and reversal. In the prevention treatment the rats received daily oral administration (mg/kg) of CVD (2.5, 5 or 7.5), saline, valproate (VAL200), or the combination of CVD5 + VAL100 for 7 days. From the 8th to 14th day LDX was added. In the reversal protocol LDX was administered for 7 days with the drugs being added from the 8th to 14th day of treatment. Two hours after the last administration the behavioral (open field and social interaction) and neurochemical (reduced glutathione, lipid peroxidation, and BDNF) determinations were performed. The results showed that CVD prevented and reversed the behavioral and neurochemical alterations induced by LDX. The administration of CVD5 + VAL100 potentiated the effect of VAL200 alone. Taken together these results demonstrate a possible antimanic effect of CVD in this preclinical model.

Synthesis and biological evaluation of hydrazone derivatives as antifungal agents.

Emerging yeasts are among the most prevalent causes of systemic infections with high mortality rates and there is an urgent need to develop specific, effective and non-toxic antifungal agents to respond to this issue. In this study 35 aldehydes, hydrazones and hydrazines were obtained and their antifungal activity was evaluated against Candida species (C. parapsilosis, C. tropicalis, C. krusei, C. albicans, C. glabrata and C. lusitaneae) and Trichosporon asahii, in an in vitro screening. The minimum inhibitory concentrations (MICs) of the active compounds in the screening was determined against 10 clinical isolates of C. parapsilosis and 10 of T. asahii. The compounds 4-pyridin-2-ylbenzaldehyde] (13a) and tert-butyl-(2Z)-2-(3,4,5-trihydroxybenzylidine)hydrazine carboxylate (7b) showed the most promising MIC values in the range of 16-32 µg/mL and 8-16 µg/mL, respectively. The compounds' action on the stability of the cell membrane and cell wall was evaluated, which suggested the action of the compounds on the fungal cell membrane. Cell viability of leukocytes and an alkaline comet assay were performed to evaluate the cytotoxicity. Compound 13a was not cytotoxic at the active concentrations. These results support the discovery of promising candidates for the development of new antifungal agents.

Phytochemistry Profile, Antimicrobial and Antitumor Potential of the Methanolic Extract of Tabernaemontana catharinensis A DC and Eragrostis plana NEES.

Natural compounds that have the potential to act as antimicrobials and antitumors are a constant search in the field of pharmacotherapy. Eragrostis plana NEES (Poaceae) is a grass with high allelopathic potential. Allelopathy is associated with compounds generated in the primary and secondary metabolism of the plant, which act to protect it from phytopathogens. Tabernaemontana catharinensis A DC (Apocynaceae), a tree in which its leaves and bark are used for the preparation of extracts and infusions that have anti-inflammatory and antinociceptive effects, is attributed to its phytochemical constitution. The objective of this study was to elucidate the phytochemical constitution, the antibacterial potential, the toxicity against immune system cells, hemolytic potential, and antitumor effect of methanolic extracts of E. plana and T. catharinensis. The phytochemical investigation was carried out using the UHPLC-QTOF MS equipment. The antibacterial activity was tested using the broth microdilution plate assay, against Gram-negative and Gram-positive strains, and cytotoxicity assays were performed on human peripheral blood mononuclear cells (PBMC) and in vitro hemolysis. Antitumor activity was performed against the colon cancer cell line (CT26). Results were expressed as mean and standard deviation and analyzed by ANOVA. p < 0.05 was considered significant. More than 19 possible phytochemical constituents were identified for each plant, with emphasis on phenolic compounds (acids: vanillic, caffeic, and quinic) and alkaloids (alstovenine, rhyncophylline, amezepine, voacangine, and coronaridine). Both extracts showed antibacterial activity at concentrations below 500 µg/mL and were able to decrease the viability of CT26 at concentrations below 2000 µg/mL, without showing cytotoxic effect on PBMCs and in vitro hemolysis at the highest concentration tested. This is the first report of the activity of E. plana and T. catharinensis extracts against colon cancer cell line (CT26). Studies should be carried out to verify possible molecular targets involved in the antitumor effect in vivo.

HPLC analysis of phenolics compounds and antioxidant capacity of leaves of Vitex megapotamica (Sprengel) Moldenke.

Vitex megapotamica (Sprengel) Moldenke belongs to the Verbenaceae family and is popularly known as "tarumã". The antioxidant capacity of fractions and crude extract from the leaves of V. megapotamica were determined in this study through the capacity to remove reactive species and phenolic compounds were quantified in the various fractions. The IC50 (DPPH) ranged from 14.17 ± 0.76 to 37.63 ± 0.98 µg/mL. The ethyl acetate fraction might contain the strongest lipid peroxidation inhibitory compounds with an IC50 of 16.36 ± 5.09 µg/mL, being also the one with the highest content of polyphenols (522.4 ± 1.12 mg/g), flavonoids (220.48 ± 0.30 mg/g) and condensed tannins (3.86 ± 0.53 mg/g). Compounds quantified by HPLC/DAD in the crude extract and fractions were chlorogenic and rosmarinic acids. Higher dosages of the extracts were more effective in reducing levels of plasma protein carbonyls and were also shown to be able to remove reactive species by a 2',7'-dichlorofluorescein diacetate assay, reducing oxidative stress in all tested fractions. Results obtained indicated that V. megapotamica exhibits good potential to prevent diseases caused by the overproduction of free radicals and it might also be used as a potential source of natural antioxidant agents.

Measurement of resistance-area product by transcranial Doppler: An alternative tool for cognitive screening in hypertensive on drug treatment?

Introduction: Arterial hypertrophy and remodeling are adaptive responses present in systemic arterial hypertension that can result in silent ischemia and neurodegeneration, compromising brain connections and cognitive performance (CP). However, CP is affected differently over time, so traditional screening methods may become less sensitive in assessing certain cognitive domains. The study aimed to evaluate whether cerebrovascular hemodynamic parameters can serve as a tool for cognitive screening in hypertensive without clinically manifest cognitive decline. Methods: Participants were allocated into groups: non-hypertensive (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. Measurements of blood pressure and middle cerebral artery blood flow velocity were obtained from digital plethysmography and transcranial Doppler. For the cognitive assessment, the Mini Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and a broad neuropsychological battery were applied. Results: Patients in groups 2 and 3 show no significant differences in most of the clinical-epidemiological variables or pulsatility index (p = 0.361), however compared to group 1 and 2, patients in group 3 had greater resistance-area product [RAP] (1.7 [±0.7] vs. 1.2 [±0.2], p < 0.001). There was a negative correlation between RAP, episodic memory (r = -0.277, p = 0.004) and cognitive processing speed (r = -0.319, p = 0.001). Conclusion: RAP reflects the real cerebrovascular resistance, regardless of the direct action of antihypertensive on the microcirculation, and seems to be a potential alternative tool for cognitive screening in hypertensive.

Phytochemical characterisation, antioxidant capacity, and in vitro toxicity of Richardia brasiliensis gomes crude extracts.

Richardia brasiliensis is a species used in folk medicine and rich in active compounds. In this study, the extracts were submitted to UHPLC-ESI-MS/MS analysis and total polyphenols, tannins, and flavonoids assays. Besides, it was determined its antioxidant capacity, oxidative stress markers and toxicological profile. Fourteen polyphenols were found and, in the dosages, a slight change in the concentrations in each extract was observed. Regarding the antioxidant capacity, the responses were different in the methods used. There was an increase in lipid peroxidation, and NO, however total ROS remained unchanged. The cells remained more than 90% viable and the extracts did not cause damage to single strands of DNA, with the exception of the crude autumn and spring extracts at 500 µg/mL. The results found in this study suggest that extracts are potentially toxic to human leukocyte cells in high concentrations; however, more studies should be performed in different cell lines.

Antioxidant Activity and phytochemical composition of the leaves of Solanum guaraniticum A. St.-Hil.

Solanum guaraniticum is a shrub belonging to the Solanaceae family popularly known in Brazil as jurubeba or false-jurubeba. The aim of this study was to evaluate the antioxidant activity of crude extract and chloroform, ethyl acetate and n-butanol fractions from its leaves, verifying the ability to remove reactive species and identify and quantify phenolic compounds. The ethyl acetate fraction showed the highest amount of total polyphenols (546.57 ± 2.35 mg gallic acid equivalent/g) and the lowest IC(50) (9.11 ± 0.75 µg/mL) by the DPPH method. Furthermore, the chloroform fraction presented the highest content of flavonoids (75.73 ± 0.34 mg rutin equivalents/g), tannins (56.03 ± 0.68 mg catechin equivalents/g) and alkaloids (10.79 ± 0.06 mg/g). This fraction was effective in the scavenging of reactive species by 2',7'-dichlorofluorescein diacetate assay, in addition to completely reducing protein carbonyl content and reducing lipid peroxidation at basal levels even at low concentrations. Chlorogenic, caffeic and rosmarinic acids were identified and quantified by HPLC/DAD. These results show that S. guaraniticum is rich in phenolic compounds and has potential as an antioxidant.

Protective effects of extracts and flavonoids isolated from Scutia buxifolia Reissek against chromosome damage in human lymphocytes exposed to hydrogen peroxide.

Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of crude extract, ethyl acetate fraction and flavonoids (quercetin, quercitrin, isoquercitrin and rutin) isolated from the leaves from Scutia buxifolia against chromosome damage induced by H2O2 in human lymphocytes by analyzing cellular growth rate, cell viability, mitotic index and chromosomal instability. We found a differential response among the compounds tested, with the ethyl acetate fraction being more effective than the crude extract, a difference perhaps related to the presence of the antioxidants identified and quantified by HPLC/DAD. In general, quercetin, isoquercitrin and rutin recovered the mitotic index and chromosomal instability more than quercitrin after treatment with hydrogen peroxide.

Sida tuberculata: In vitro cytotoxicity and in vivo anti-inflammatory effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Sida tuberculata R. E. Fries (Malvaceae) is a pioneer species considered a weed in farm fields in Southern Brazil. Widely distributed in South Brazil, S. tuberculata is popularly used to treat inflammatory conditions. AIMS OF THE STUDY: The current study aimed to assess the in vitro cytotoxic and in vivo anti-inflammatory properties of S. tuberculata. MATERIALS AND METHODS: Initially, extracts obtained from leaves (STLE) and roots (STRE) were submitted to cytotoxicity tests using human leukocytes (non-malignant cell line) and HepG2 and MCF-7 (tumor cell lines). In sequence, anti-inflammatory properties were investigated against carrageenan-induced peritonitis model. RESULTS: In vitro analyses displayed a significant decrease in human leukocytes viability without genotoxic damage. IC50 results from tumor cells presented significant decrease in cell viability, slightly more pronounced for STRE. In addition, STLE significantly inhibited the inflammatory and oxidative parameters (TBARS, NPSH, SOD, MPO activity, cell influx, and cytokines release). CONCLUSION: Our findings indicate S. tuberculata extracts have cytotoxic potential more pronounced on tumor cell lines, as well as leaves extract shows a significant reduction in acute inflammation process, as already reported for Sida genus and specifically for this species.

Habitual intake of guaraná and metabolic morbidities: an epidemiological study of an elderly Amazonian population.

The aim of the present study was to evaluate the associations of metabolic disorders and anthropometric and biochemical biomarkers of lipid, glucose and oxidative metabolism and the habitual ingestion of guaraná (Paullinia cupana, Mart. Var. sorbilis) by an elderly population residing in the Amazon Riverine region of the Maués municipality (Brazil). A case-controlled study was performed that included 637 elderly (≥60 years of age) patients classified as either those who habitually drank guaraná (GI, n = 421) or those who never drank guaraná (NG, n = 239) based upon their self-reported intake of guaraná. Indeed, the prevalence of various metabolic disorders was associated with guaraná ingestion. The prevalence of hypertension, obesity and metabolic syndrome in the GI group was lower than the prevalence found in the NG group. The NG group exhibited lower systolic and diastolic blood pressure values. The males in the GI group exhibited a lower waist circumference, on average, than the circumference found in the NG group, whereas the females in the GI group had lower cholesterol (total and LDL-c) levels than the control cohort. Additionally, a significant association was found between lower levels of advanced oxidative protein product (AOPP) and habitual guaraná consumption. The results constitute the first epidemiological study to suggest a potentially protective effect of habitual guaraná ingestion against metabolic disorders in elderly subjects.

Evaluation In Vitro of Toxicity of Hydroalcoholic Extract of Leaves and Roots from Yacon (Smallanthus sonchifolius).

Yacon is an Andean plant that has been used in folk medicine for its medicinal properties. The beneficial effects of this plant are possibly due to the high content of phenolic compounds present in its leaves and roots. This study evaluated the in vitro toxicity of the hydroalcoholic extract of leaves and roots from yacon (1, 10, 50, and 100 µg/mL) through cell viability tests, genotoxic and mutagenic activity in leukocytes culture cells; and cytotoxicity and apoptosis cell death (1, 10, 50, 100, and 500 µg/mL) in cell line originally established from the primary mouse embryonic fibroblast cells that were cultured by the designated protocol, so-called 3T3 protocol "3-day transfer, inoculum 3 × 105 cells" (3T3 cell line). No mutagenic and cytotoxic activities were observed in leukocyte cultures. Cytotoxic activity was evidenced in the highest concentrations of yacon leaf extract (50 and 100 µg/mL), whereas all concentrations tested with yacon leaf extract there was induction for apoptosis in the 3T3 cells. Genotoxic potential was observed only at higher doses of leaf (50 and 100 µg/mL) and root (100 µg/mL) extract. These results suggest that yacon leaf at high concentrations may present toxic potential showing concentration-dependent behavior; however, in vivo studies should be performed to validate these results.

The use of fructose as a sweetener. Is it a safe alternative for our immune system?

Fructose is a constituent of sucrose and other polymers referred to as inulin or fructans. We can find in cereals, vegetables, and honey. It has the property of being 1.5 times sweeter than sucrose. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. For this purpose, we made use of lymphocyte cultures and the analysis of their CD4+ and CD8+ subpopulations. Computational methods propose the mechanism of action. Our data showed a reduction in all lymphocyte subfractions evaluated, resulting in a reduction in total lymphocytes, as well as an increase in the DNA damage of cells exposed to fructose. It was possible to propose that fructose modulates gene expression, mainly interfering with the MAPK8, APTX, TUBGCP3, and LST1 genes. Although fructose is used globally as a sweetener, its use should be cautious, as our study points out that it has cytotoxic and genotoxic effects. PRACTICAL APPLICATIONS: Fructose is one of the most sold and used sweeteners in the world. We show here that its use must be restricted and used carefully because it can alter the gene expression and also interfere with cellular and genetic metabolism and may even interfere with the immune response.

Fumonisin B1 induces toxicity in human leukocytes at low concentrations: Are computational studies effective to determine biosafety?

Fumonisin B1 is a mycotoxin produced by Fusarium verticillioides and Fusarium proliferatum found in various crops, particularly maize. Besides carcinogenicity, other manifestations have been registered in different animals and in humans. In the case of humans, epidemiological studies have reported high prevalence of esophageal cancer in populations exposed to fumonisins. This study aimed to evaluate the minimum concentration of FB1 capable of inducing cytotoxicity (cell viability test), genotoxicity (comet assay) and mutagenicity (micronucleus) in cultured human leukocytes and to evaluate the effectiveness of in silico tests to predict FB1 toxicity. All concentrations analyzed (200; 100; 50; 5; 0.5; 0.05; 0.005 µg/mL and 300; 30; 3; 1; 0.1; 0.01 fg/mL) except the lowest demonstrated dose-dependent toxicity in all parameters analyzed (p < 0.05 to p < 0.0001). As for predictions, only the Lazar software showed carcinogenicity of FB1 for rats. Thus, it is evident that FB1 is able to induce dose-dependent damage at low concentrations, and that computational tests, although desirable for prediction, are not effective as biological tests to determine toxicity, at least of FB 1 and within the experimental conditions tested.

Systemic arterial hypertension and cognition in adults: effects on executive functioning.

BACKGROUND: Central nervous system changes associated to systemic arterial hypertension (SAH) are progressive and may cause negative effects on cognitive performance. The objective of this study was to investigate the relation between SAH and the components of executive functions (EF), inhibitory control (IC), updating and shifting, comparing a control group (without SAH) to patients with SAH, in two levels of severity. METHODS: The protocol included the following tests to evaluate EF components: T.O.V.A. Test (IC), Backward Digit Span from Wechsler Adults Intelligence Scale (WAIS-III), Phonemic and Semantic Verbal Fluency (updating), and Trail Making Test Part B (shifting). RESULTS: A total of 204 participants was included: 56 from the Control Group (CG), 87 SAH stage 1, and 61 SAH stage 2. The groups were not different for age (52.37±12.29) and education (10.98±4.06). As to controlled blood pressure (BP), duration of hypertension treatment and number of drugs, the SAH 2 group had a worse BP control, longer duration of hypertension treatment and use of more drugs when compared to the SAH 1. The findings revealed that patients with more severe hypertension presented worse performance in updating (Backward Digit Span, phonemic and semantics VF) and shifting (Trail Making Test Part B). CONCLUSION: The results suggest that patients with SAH have a significant impairment in EF, more specifically in updating and shifting. Besides that, such damage may be directly proportional to the severity of SAH. It is suggested that future studies include neuroimaging exams to exclude possible cerebrovascular diseases.