Effects of calcium supplementation on changes in the IL2, IL4, IL6, IL10 axes and oxidative stress in pregnant women at risk for pre-eclampsia.

BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Phytochemical profiling, antidiabetic, antitumoral and cytotoxic potential of Psidium cattleianum Afzel. ex Sabine leaves of red variety.

In this study, phytochemical profiling, and antidiabetic, antitumoral and cytotoxic potential of aqueous extracts of leaves of red variety of Psidium cattleianum Afzel. ex Sabine were investigated. The extracts were obtained using a cellulase complex. The total phenolic compounds (TPC) were determined, and the individual phenolic compounds were quantified by HPLC-ESI-MS/MS. For the TPC, the amounts varied from 85.91 to 106.33 mg EAG g-1. Eighteen compounds have been identified. The compounds with the highest concentrations were gallic acid, quercetin and protocatechuic acid. Antidiabetic activity was obtained through α-amylase and α-glucosidase inhibition tests. The extract inhibited 17.94% of α-amylase activity and 73.34% of α-glucosidase activity. The antitumoral activity in cells of cutaneous melanoma (SK-MEL-28) and the cytotoxic activity was determined in peripheral blood mononuclear cells (PBMC). The cellular migration was determined for cells SK-MEL-28. Antitumoral effects on cells SK-MEL-28 were observed and the absence of cytotoxicity on the PBMCs.

Oxidative stress in Hashimoto's thyroiditis: possible adjuvant therapies to attenuate deleterious effects.

A number of studies have shown that oxidative stress is related to the pathogenesis of several immunological diseases, such as Hashimoto's thyroiditis (HT), although there is no plausible mechanism to explain it. Thus, we aimed at hypothesizing and providing some possible mechanisms linking oxidative stress to autoimmunity aspects and its implications for HT, as well as adjuvant therapeutic proposals to mitigate the deleterious effects. Our hypothesis is that deficient eating habits, autoimmune regulator gene predisposing gene, dysbiosis and molecular mimicry, unfolded proteins and stress in the endoplasmic reticulum, and thymus involution appear to be the main potential factors leading to HT oxidative stress. Likewise, we show that the use of minerals selenium and zinc, vitamins D and C, as well as probiotics, can be interesting adjuvant therapies for the control of oxidative damage and poor prognosis of HT. Further clinical trials are needed to understand the real beneficial and side effects of these supplements.

Role of inflammation and oxidative stress in tissue damage associated with cystic fibrosis: CAPE as a future therapeutic strategy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

Supplementation with detox juice added with probiotic improves atherogenic parameters in healthy individuals

Abstract Phytochemicals present in detox juices and probiotics have demonstrated protective effects on cardiovascular risk factors. The consumption of these products alone modulate metabolic mechanisms and biomarkers. However, the effects of the combination of detox juice and probiotics have not yet been evaluated on atherogenic parameters. A randomized controlled study was carried out with 40 healthy volunteers (20 men and 20 women), aged between 18 and 50 years old. The volunteers ingested 200mL of juice for 30 days. Before and after supplementation, the anthropometric and lipid profiles and plasma concentrations of TBARS, Myeloperoxidase, Glutathione, Protein and non-protein Thiols and Vitamin C were analyzed. A reduction in LDL-c (p=0.05), triglycerides (p=0.05) and a significant increase in HDL-c (p=0.002) was observed. There was a significant decrease in the concentrations of TBARS (p=0.01), myeloperoxidases (p=0.02) and a significant increase in the Vitamin C and GSH (p=0.01). There wasn`t improvement in anthropometric parameters and total cholesterol. The findings highlight that supplementation with probiotic detox juice improves the lipid and antioxidant profile, suggesting a possible positive effect in reducing the risk of cardiovascular disease in healthy volunteers. Nevertheless, more robust researches with a prolonged treatment period should be conducted.

Tucumã (Astrocaryum aculeatum) Prevents Oxidative and DNA Damage to Retinal Pigment Epithelium Cells.

Eye diseases have a negative impact on the eyesight quality of the world population. The age-related macular degeneration (AMD) draws special attention since it is a chronic disorder characterized by oxidative and inflammatory damage to the retinal epithelial pigment, which triggers progressive vision loss. In the Brazilian Amazon, Astrocaryum aculeatum is an Amazonian fruit (Tucumã) used by riverside communities in traditional medicine to treat a number of ailments. These communities have recently shown to have increased longevity and reduced prevalence of age-related morbidity. Thus, the aim of this research was to chemically characterize and analyze the in vitro antioxidant effect and molecular damage prevention of the Tucumã ethanolic extract in retinal pigment epithelium (RPE) cells in a model for AMD. The extract was chemically characterized by ultra-high-performance liquid chromatography (HPLC) coupled with diode-array detection and mass spectrophotometry (HPLC-DAD-MS). In vitro protocols were performed, and the cytopreventive effect of Tucumã on RPE cells exposed to high concentrations of superoxide anion, an oxidant and genotoxic molecule, as well as the effect of Tucumã extract on oxidative and molecular makers were assessed. Biochemical and flow cytometry analyses were conducted in these protocols. The extract presents high concentrations of caffeic acid, gallic acid, catechin, luteolin, quercetin, and rutin. Treatment did not show cytotoxic effects in cells treated only with extract at 50 µg/mL. In fact, it improved cell viability and was able to prevent necrosis and apoptosis, and oxidative and molecular damage was significantly reduced. In summary, Tucumã is an important Amazon fruit, which seems to contribute significantly to improve human health conditions, as our findings suggest that its extract has a relevant chemical matrix rich in antioxidant molecules, and its consumption could improve eye health and contribute to prevention against oxidative stress through cytoprevention, reactive oxygen species reduction, and maintenance of DNA integrity in retinal pigment epithelium (RPE) cells.

Antihyperglycemic activity of crude extract and isolation of phenolic compounds with antioxidant activity from Moringa oleifera Lam. leaves grown in Southern Brazil.

The antihyperglicemic activity of crude extract from Moringa oleifera leaves and isolation of phenolic compounds with antioxidant activity using bioguided assay were employed by the first time in leaves cultivated in Brazil. The hydroalcoholic extract (HE) was produced by using ethanol:water (80:20 v/v) and purified by solid-liquid procedure using solvents in ascending order of polarity. The ethyl acetate fraction (Fr-EtOAc) presented high antioxidant potential and it was purified using chromatographic techniques rendering isolated compounds that were identified from the spectral data. The HE extract (500 mg kg-1) was adimistrated in diabetic rats induced by streptozotocin and chemical markers and lipid peroxidation in liver and kidney were evaluated. The Fr-EtOAc showed high antioxidant potential by FRAP reduction method (1678 µmol Fe2+ g-1), DPPH and ABTS scavenging methods (526.7 and 671.5 µmol TEAC g-1 respectively) and ORAC assay (3560.6 µmol TEAC g-1). Therefore, the Fr-EtOAc was purified and yielded three bioactive subfractions (S-12, S-13 abd S-15) that were rechromatoghaphed in HPLC-SemiPrep. After that, two main bioactive glycosylated flavonoids (isoquercitrin and astragalin) and phenolic acid (3-O-caffeoylquinic acid) were obtained. Additionally, the HE extract provided protection against oxidative damage in liver and kidney of diabetic rats ameliorating endogenous antioxidant defenses by increase catalase (CAT), glutathione S-transferase (GST) and non-protein thiol groups (NPSH) levels as well as decreased the lipid peroxidation in these tissues. Our results indicate that three phenolic compounds with high antioxidant activity were isolated and, the chemical composition of HE crude extract, rich in flavonoids glycosylated could be intimately related to antihyperglycemic action. So, it is possible to suggest that these compounds may be used as chemical biomarkers for this plant in Brazil, ensuring quality and supporting the use of aerial parts in tradicional medicine.

Effect of Scutia buxifolia Reissek in nucleotidase activities and inhibition of platelet aggregation.

This study aimed to determine the effect of lyophilized aqueous extracts of Scutia buxifolia on NTPDase and 5'-nucleotidase activity on platelets and lymphocytes as well as the profile of the platelet aggregation. In vitro tests were used to investigate the effect of the aqueous crude extract obtained from S. buxifolia leaves (SbL) and stem bark (SbS) on enzymatic activities and platelet aggregation. The platelets and lymphocytes were exposed to lyophilized aqueous extracts of S. buxifolia at concentrations of 1-200 µg/mL in the presence of ATP, ADP, AMP as substrates, during the enzymatic assay, as well as the platelet aggregation. The results showed that SbS and SbL potently inhibited NTPDase and 5'-nucleotidase in platelets and lymphocytes. ADP-induced aggregation was inhibited by the SbS (50, 100, and 200 µg/mL) and SbL (200 µg/mL). In addition, these results suggest that S. buxifolia have compounds, such as gallic acid, chlorogenic acid, caffeic acid, quercetin, rutin, and kaempferol, which cause a decrease the NTPDase and 5'-nucleotidase activity, resulting in alterations in adenine nucleotide levels and protection against ADP-induced platelet aggregation.

Cytotoxic effects of infusions (tea) of Solidago microglossa DC. (Asteraceae) on the cell cycle of Allium cepa / Efeitos citotóxicos das infusões (chá) de Solidago microglossa DC. (Asteraceae) no ciclo celular de Allium cepa

The medicinal specie Solidago microglossa DC., which is native from South America, is used as infusion (tea) for stomach disorders in popular medicine. This study aimed to evaluate the potential cytotoxic effect of these infusions on the cell cycle of Allium cepa. In natura leaves of three populations of this species were used in preparing infusions at two concentrations: 1.75 mg/mL and 14 mg/mL. Onion (Allium cepa) root-tip cells were used as test system in in vivo assays. Slides were done through smashing technique. Cells were analyzed in all cell cycles of A. cepa, totalizing 6000 cells for each group of bulbs. The mitotic index (MI) was calculated, and the statistical analysis was carried out through the Chi-square test (χ2 = 0.05). The results show that the infusions of S. microglossa at a highest concentration (14 mg/mL) caused a significant reduction in the MI compared with control in the studied populations. In concentrations commonly used by people there was a significant increase of MI in relation to controlled populations 1 and 3 and a decrease in population 2. In conclusion, infusions of S. microglossa presented antiproliferative effect at a highest concentration.

A espécie medicinal Solidago micrglossa DC., a qual é nativa da América do Sul, é usada como infusão (chá) para desordens estomacais na medicina popular. O objetivo desse estudo foi avaliar o potencial efeito citotóxico dessas infusões no ciclo celular de Allium cepa. Folhas in natura de três populações dessa espécie foram utilizadas no preparo das infusões em duas concentrações: 1,75 mg/mL e 14 mg/mL. Células de raízes de cebola (Allium cepa) foram usadas como sistema teste nos ensaios in vivo. As lâminas foram feitas através da técnica de esmagamento. As células foram analisadas em todos os ciclos celulares de A. cepa, totalizando 6000 células para cada grupo de bulbos. O índice mitótico (IM) foi calculado e a análise estatística foi realizada através do teste Qui-quadrado (χ2 = 0,05). Os resultados mostraram que as infusões de S. microglossa na maior concentração (14 mg/mL) causou uma redução no IM comparado com os controles nas populações estudadas. Nas concentrações comumente usadas pelas pessoas houve um aumento significativo do IM em relação ao controle nas populações 1 e 3 e foi reduzido na população 2. Em conclusão, infusões de S. microglossa apresentam efeito antiproliferativo na maior concentração testada.

Uso do sistema teste de Allium cepa como bioindicador de genotoxicidade de infusões de plantas medicinais / The use of Allium cepa test as a bioindicator of genotoxicity of medicinal plants infusions

Mundialmente, muitas espécies de plantas medicinais são utilizadas para o tratamento de doenças. No entanto, a maioria dessas espécies não foram suficientemente estudadas, principalmente quanto à presença de substâncias citotóxicas/mutagênicas em sua composição ou decorrentes do próprio metabolismo e podem causar danos à saúde da população. A presença de substâncias mutagênicas nas espécies vegetais que causam alterações cromossômicas podem ser detectadas durante o ciclo celular de uma espécie. O sistema teste de Allium cepa é freqüentemente utilizado para avaliação do potencial genotóxico de extratos de plantas medicinais através da análise de células meristemáticas provenientes de pontas de raízes tratadas com infusões medicinais (chás). O conhecimento do potencial genotóxico destas espécies medicinais, através da análise do ciclo celular de Allium cepa serve como indicativo de segurança para a população que utiliza chás medicinais como única alternativa para o tratamento de doenças. Essa revisão, objetiva informar a respeito da importância do teste de Allium cepa para avaliação preliminar da genotoxicidade de infusões de plantas medicinais.

All over the world, many species of medicinal plants are used for disease treatments. However, most of them were not deeply studied; and the presence of cytotoxic or mutagenic substances in their composition or resulting from their metabolism may be harmful to human beings. The mutagenic effects caused by such substances result in chromosomal changes which are detecTable during the cell cycle of a species through cytogenetic analysis. The Allium cepa test system is widely used for evaluating the genotoxic potential of infusions (tea) made of medicinal plants, through the cell cycle analysis. The knowledge of the genotoxic potential of such species through the Allium cepa test serves as a warning and safety bioindicator for the population who uses medicinal tea quite often as the unique alternative for disease treatment of its people. In the review article, we intend to inform people about the importance of the Allium cepa test for evaluating the genotoxicity of infusions of medicinal plants.