Proteins are important targets of several modifications caused by oxidative stress, leading to st... more Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities ...
Introduction: With aging, there is gradual loss of muscle mass volume, accounting for almost all ... more Introduction: With aging, there is gradual loss of muscle mass volume, accounting for almost all the loss of strength in the elderly. Studies have shown that physical activity can reduce morbidity from cardiovascular disease, stroke and increase the autonomy and independence. Objective: To examine the association among levels of physical activity, cardiovascular risk and gene polymorphism of E Apolipoprotein in the elderly. Methods: retrospective study, from an observational database on a population that selected sedentary seniors with a history of regular physical activity, carriers and noncarriers of the e4 allele of the gene of E Apolipoprotein. We applied the following questionnaires: (a) International Physical Activity Questionnaire (IPAC), (b) 24-hour recall and mini-food frequency questionnaire, (c) biochemical analysis of lipids and glucose levels. Results: 255 elderly were investigated. Of these, 51 (20%) were men and 204 women (80%); 5.9 years of age (minimum 60 maximum 86...
Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a prote... more Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the treatment of breast cancer. To perform this study, MCF-7 breast cancer cells were cultured under controlled conditions and exposed to 1, 5 and 10 µg/ml guarana concentrations, with and without chemotherapeutics (gemcitabine, vinorelbine, methotrexate, 5-fluorouracil, paclitaxel, doxorubicin and cyclophosphamide). The effect of these treatments on MCF-7 cell viability and proliferation was spectrophotometrically analyzed with the MTT assay. The main results demonstrated an antiproliferative effect of guarana at concentrations of 5 and 10 µg/ml and a significant effect on chemotherapeutic drug action. In general, guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggested an interaction of guarana with the chemotherapeutic drugs, which requires confirmation by in vivo complementary studies.
This study quantifies the bioactive molecules in and determines the in vitro protective effect of... more This study quantifies the bioactive molecules in and determines the in vitro protective effect of ethanolic extracts isolated from the peel and pulp of tucumã (Astrocaryum aculeatum, Mart.), an Amazonian fruit rich in carotenoids. The cytoprotective effect of tucumã was evaluated in lymphocyte cultures exposed to H 2 O 2 using spectrophotometric, fluorimetric, and immunoassay assays. The results confirmed that tucumã pulp extract is rich in b-carotene and quercetin, as previously described in the literature. However, high levels of these compounds were also found in tucumã peel extract. The extracts also contained significant amounts rutin, gallic acid, caffeic acid, and chlorogenic acid. Despite quantitative differences in the concentration of these bioactive molecules, both extracts increased the viability of cells exposed to H 2 O 2 in concentrations ranging from 300 to 900 lg/mL. Caspases 1, 3, and 8 decreased significantly in cells concomitantly exposed to H 2 O 2 and these extracts, indicating that tucumã cryoprotection involves apoptosis modulation.
Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mese... more Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mesenchymal stem cells, often making them unviable in regenerative clinical practice. In vitro supplementation by antioxidant food extract of senescent mesenchymal stem cells could reverse these undesirable characteristics. To evaluate this hypothesis, senescent adipocyte-mesenchymal cells (ASCs) obtained from human lipoaspirates were exposed at different concentrations of hydro-alcoholic guaraná (Paullinia cupana) extract for 72 h. After the incubation, we performed a proliferative assay. Oxidative stress indicators and antioxidant enzymes (biochemical activity and gene expression by qRT-PCR analysis) in these senescent cells were also evaluated. In senescent cells exposed to guaraná at 5 mg/g concentration increased cellular proliferation occurred compared to untreated senescent cells (79.1 ± 15.7%). Concomitantly, a decrease in several oxidative stress indicators was observed in senescent cells treated with guaraná. A genomic effect of guaraná exposure was observed when the modulation of antioxidant enzymes genes was analyzed. The results described here suggest that the food extract supplementation could reverse the initial senescence processes in ASCs. These results have potential application in regenerative medicine.
Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been us... more Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1-3), and nine benzophenanthridine alkaloids (4-12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group.
Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and ... more Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2) gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs) obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM)...
The present study investigated the effects of quercetin in the impairment of memory and anxiogeni... more The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na + ,K + -ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5 mg/kg) and quercetin (5, 25 or 50 mg/kg) by gavage for 45 days. Animals were divided into eight groups (n = 10-14): saline/control, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg and Cd/Querc 50 mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na + ,K + -ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na + ,K + -ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cdexposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na + ,K + -ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.
Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and anti... more Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and antioxidant defenses. Two main antioxidant systems exist. The nonenzymatic system relies on molecules to directly quench ROS and the enzymatic system is composed of specific enzymes that detoxify ROS. Among the latter, the superoxide dismutase (SOD) family is important in oxidative stress modulation. Of these, manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location, i.e., the main site of superoxide (O 2 •À ) production. As such, extensive research has Advances in Clinical Chemistry, Volume 68 # 2015 Elsevier Inc.
Revista Brasileira de Geriatria e Gerontologia, 2011
Methods -We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veran... more Methods -We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veranópolis. We used the gene amplification technique through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The most frequent genotypes were compared considering biological variables and cardiovascular risks and morbidity.
Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there a... more Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there are growing numbers of smokers who continue to smoke at a low daily rate, or less frequently (non-daily smokers). This group needs to be better characterized in order to direct preventive actions and public health policies. The aim here was to compare lifestyle, health characteristics and alcoholism problems among young adult smokers, non-daily smokers and non-smokers. This was a cross-sectional study in which volunteers from the university community and its surrounds in Santa Maria, State of Rio Grande do Sul, Brazil, were included between October 2007 and January 2008. Out of 1240 volunteers initially contacted in a university cafeteria, a total of 728 participants of mean age 22.45 ± 3.32 years were selected for final analysis. Data were collected using structured questionnaires. In general, it was observed that the non-daily smokers showed intermediate characteristics in relation to the smokers and non-smokers. However, there was a significant association between non-daily smoking and alcohol abuse. The non-daily smokers presented an odds ratio of 2.4 (95% confidence interval: 1.10-5.48) in relation to the daily smokers and an odds ratio of 3.3 (confidence interval: 1.7-6.5) in relation to the non-smokers, with regard to presenting a positive CAGE test, thereby indicating alcohol abuse or dependence. The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.
The aim of the present study was to evaluate the associations of metabolic disorders and anthropo... more 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. a Agricultural and fishing activities; comparison between categorical variables were performed by Chi-square statistical test.
Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of micr... more Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of microorganisms. These proprieties are relevant mainly in tropical areas, as Amazonian region where infectious are highly prevalent. Therefore, this study investigated the antimicrobial activity of tucumã Amazonian fruit against 37 microorganisms. The potential role of oxidative metabolism imbalance was also studied as causal mechanism of antimicrobial activity. The results showed antibacterial effect of pulp and peel tucumã hydro-alcoholic extracts on three Gram-positive bacteria (Enterococcus faecalis, Bacillus cereus, Listeria monocytogenes) and antifungal effect against Candida albicans. The antimicrobial contribution of main chemical compounds (quercetin, rutin, β-carotene and gallic, caffeic and chlorogenic acids) found in tucumã extracts was also investigated showing an inhibitory effect depending of the organism mainly by quercetin in bacteria and rutin in C. albicans. Analysis of kinetic of DNA releasing in extracellular medium by fluorescence using DNA Pico Green assay(®) and reactive oxygen species production (ROS) showed potential oxidative imbalance contribution on tucumã inhibitory effect. In B. cereus and C. albicans this effect was clear since after 24h the ROS levels were higher when compared to negative control group. In conclusion, tucumã extracts present antimicrobial activity to four microorganisms that have large problems of drug resistance, and the possible mechanism of action of this Amazon fruit is related to REDOX imbalance.
Background: Previous experimental investigations have suggested that guaraná (Paullinia cupana Ku... more Background: Previous experimental investigations have suggested that guaraná (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guaraná on LDL and serum oxidation. Methods: The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guaraná (GI) or never ingested guaraná (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guaraná in their diets. The LDL samples were exposed to 5 different guaraná concentrations (0.05, 0.1, 0.5, 1, and 5 μg/mL).
Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Gran... more Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Grande do Sul (Southern Brazil) and has been used in Brazilian traditional medicine as antiseptic and antimicrobial for the treatment of many different health problems as well as to treat leucorrhea and to assist in ulcer and wound healing. Although it is a plant widely used by the population, there are no studies proving this popular use. The crude aqueous extract, the crude neutral methanol extract, fractions prepared from this extract (n-hexane, ethyl acetate, and n-butanol), pure compounds isolated from these fractions, and derivatives were investigated in vitro for antimicrobial activities against five Gram positive bacteria: Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, three Gram negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei, and four yeasts: Candida albicans, Candida tropicalis, Cryptococcus neoformans, and Saccharomyces cerevisiae. The isolated compound moronic acid, which is the most active, was tested against a range of other bacteria such as two Gram positive bacteria, namely, Bacillus cereus, Enterococcus spp, and six Gram negative bacteria, namely, Burkholderia cepacia, Providencia stuartii, Morganella morganii, Enterobacter cloacae, Enterobacter aerogenes, and Proteus mirabilis. The leaf aqueous extract (decoction) of Schinus lentiscifolius showed a broad spectrum of antibacterial activity, ranging from 125 to 250 μg/ml (MIC) against the tested bacteria and fungi. The n-hexane extract, despite being very little active against bacteria, showed an excellent antifungal activity, especially against Candida albicans (MIC=25 μg/ml), Candida tropicalis (MIC=15.5 μg/ml), and Cryptococcus neoformans, (MIC=15.5 μg/ml). From the acetate fraction (the most active against bacteria), compounds 1-6 were isolated: nonadecanol (1), moronic acid (2), gallic acid methyl ester (3), gallic acid (4), quercetin (5) and quercitrin (6). The minimal inhibitory concentration (MIC) of moronic acid between 1.5 and 3 μg/ml against most of the tested bacteria shows that it is one of the metabolites responsible for the antibacterial activity of Schinus lentiscifolius. The antimicrobial activity and some constituents of Schinus lentiscifolius are reported for the first time. The results of the present study provide scientific basis for the popular use of Schinus lentiscifolius for a number of different health problems.
The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Ma... more The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240 mg/g, theobromine = 6.733 mg/g and total catechins = 4.336 mg/g. Cells were exposed to 10 lM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.
The effect of guaraná on cytokine levels was also evaluated in culture medium supplemented with g... more The effect of guaraná on cytokine levels was also evaluated in culture medium supplemented with glucose and insulin. a randomised, placebo-controlled in vivo assay was also performed to evaluate the potential influence of guaraná on the blood cytokine levels of 14 healthy volunteers supplemented for 14 days. The effect of guaraná was similar to that of resveratrol, a known anti-inflammatory molecule, decreasing Il-1β, Il-10 and Ig-γ levels and increasing Il-10 levels compared to those of the control group. The in vitro insulin supplementation potentiated the effect of guaraná on some cytokines. a decreasing effect on the blood inflammatory cytokine levels, along with an increase in Il-10 levels, was also observed in volunteers supplemented with guaraná. In conclusion, guaraná positively modulates cytokines associated with inflammatory metabolism.
Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative ... more Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O À 2 ). The superoxide dismutase manganese dependent (SOD2) catalyzes O À 2 in H 2 O 2 into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-a, IFN-c). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question.
Objectives: To investigate the association of the + 3953 IL-1B gene polymorphism in healthy subje... more Objectives: To investigate the association of the + 3953 IL-1B gene polymorphism in healthy subjects with serum oxidized LDL (oxLDL) levels.
Proteins are important targets of several modifications caused by oxidative stress, leading to st... more Proteins are important targets of several modifications caused by oxidative stress, leading to structural changes and consequently partial or total loss of their functions. The oxidized proteins include advanced oxidation protein products (AOPP) derived from oxidation-modified albumin, as well as fibrinogen and lipoproteins. An increase in AOPP levels indicates an oxidative stress state and the presence of coexisting inflammation. Several investigations have also suggested an association between high AOPP levels and aging-related diseases. However, the link between elevated AOPP levels and elderly mortality risk has not yet been investigated. Here, we report on a 5-year longitudinal study that investigated the potential association between AOPP levels and mortality using a population-based representative sample of riparian elders living in Brazilian Amazon region (Maués-AM). Age, sex, socioeconomic and cultural conditions, chronic morbidities, polypharmacy, and previous morbidities ...
Introduction: With aging, there is gradual loss of muscle mass volume, accounting for almost all ... more Introduction: With aging, there is gradual loss of muscle mass volume, accounting for almost all the loss of strength in the elderly. Studies have shown that physical activity can reduce morbidity from cardiovascular disease, stroke and increase the autonomy and independence. Objective: To examine the association among levels of physical activity, cardiovascular risk and gene polymorphism of E Apolipoprotein in the elderly. Methods: retrospective study, from an observational database on a population that selected sedentary seniors with a history of regular physical activity, carriers and noncarriers of the e4 allele of the gene of E Apolipoprotein. We applied the following questionnaires: (a) International Physical Activity Questionnaire (IPAC), (b) 24-hour recall and mini-food frequency questionnaire, (c) biochemical analysis of lipids and glucose levels. Results: 255 elderly were investigated. Of these, 51 (20%) were men and 204 women (80%); 5.9 years of age (minimum 60 maximum 86...
Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a prote... more Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the treatment of breast cancer. To perform this study, MCF-7 breast cancer cells were cultured under controlled conditions and exposed to 1, 5 and 10 µg/ml guarana concentrations, with and without chemotherapeutics (gemcitabine, vinorelbine, methotrexate, 5-fluorouracil, paclitaxel, doxorubicin and cyclophosphamide). The effect of these treatments on MCF-7 cell viability and proliferation was spectrophotometrically analyzed with the MTT assay. The main results demonstrated an antiproliferative effect of guarana at concentrations of 5 and 10 µg/ml and a significant effect on chemotherapeutic drug action. In general, guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggested an interaction of guarana with the chemotherapeutic drugs, which requires confirmation by in vivo complementary studies.
This study quantifies the bioactive molecules in and determines the in vitro protective effect of... more This study quantifies the bioactive molecules in and determines the in vitro protective effect of ethanolic extracts isolated from the peel and pulp of tucumã (Astrocaryum aculeatum, Mart.), an Amazonian fruit rich in carotenoids. The cytoprotective effect of tucumã was evaluated in lymphocyte cultures exposed to H 2 O 2 using spectrophotometric, fluorimetric, and immunoassay assays. The results confirmed that tucumã pulp extract is rich in b-carotene and quercetin, as previously described in the literature. However, high levels of these compounds were also found in tucumã peel extract. The extracts also contained significant amounts rutin, gallic acid, caffeic acid, and chlorogenic acid. Despite quantitative differences in the concentration of these bioactive molecules, both extracts increased the viability of cells exposed to H 2 O 2 in concentrations ranging from 300 to 900 lg/mL. Caspases 1, 3, and 8 decreased significantly in cells concomitantly exposed to H 2 O 2 and these extracts, indicating that tucumã cryoprotection involves apoptosis modulation.
Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mese... more Cellular senescence is a limiting factor in the proliferative expansion and quality of adult mesenchymal stem cells, often making them unviable in regenerative clinical practice. In vitro supplementation by antioxidant food extract of senescent mesenchymal stem cells could reverse these undesirable characteristics. To evaluate this hypothesis, senescent adipocyte-mesenchymal cells (ASCs) obtained from human lipoaspirates were exposed at different concentrations of hydro-alcoholic guaraná (Paullinia cupana) extract for 72 h. After the incubation, we performed a proliferative assay. Oxidative stress indicators and antioxidant enzymes (biochemical activity and gene expression by qRT-PCR analysis) in these senescent cells were also evaluated. In senescent cells exposed to guaraná at 5 mg/g concentration increased cellular proliferation occurred compared to untreated senescent cells (79.1 ± 15.7%). Concomitantly, a decrease in several oxidative stress indicators was observed in senescent cells treated with guaraná. A genomic effect of guaraná exposure was observed when the modulation of antioxidant enzymes genes was analyzed. The results described here suggest that the food extract supplementation could reverse the initial senescence processes in ASCs. These results have potential application in regenerative medicine.
Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been us... more Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1-3), and nine benzophenanthridine alkaloids (4-12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect considering the decrease in TBARS and AOPP (advanced oxidized protein products) levels when compared to the control group.
Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and ... more Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2) gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs) obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM)...
The present study investigated the effects of quercetin in the impairment of memory and anxiogeni... more The present study investigated the effects of quercetin in the impairment of memory and anxiogenic-like behavior induced by cadmium (Cd) exposure. We also investigated possible alterations in acetylcholinesterase (AChE), Na + ,K + -ATPase and δ-aminolevulinate dehydratase (δ-ALA-D) activities as well as in oxidative stress parameters in the CNS. Rats were exposed to Cd (2.5 mg/kg) and quercetin (5, 25 or 50 mg/kg) by gavage for 45 days. Animals were divided into eight groups (n = 10-14): saline/control, saline/Querc 5 mg/kg, saline/Querc 25 mg/kg, saline/Querc 50 mg/kg, Cd/ethanol, Cd/Querc 5 mg/kg, Cd/Querc 25 mg/kg and Cd/Querc 50 mg/kg. Results demonstrated that Cd impaired memory has an anxiogenic effect. Quercetin prevented these harmful effects induced by Cd. AChE activity decreased in the cerebral cortex and hippocampus and increased in the hypothalamus of Cd-exposed rats. The Na + ,K + -ATPase activity decreased in the cerebral cortex, hippocampus and hypothalamus of Cd-exposed rats. Quercetin prevented these effects in AChE and Na + ,K + -ATPase activities. Reactive oxygen species production, thiobarbituric acid reactive substance levels, protein carbonyl content and double-stranded DNA fractions increased in the cerebral cortex, hippocampus and hypothalamus of Cdexposed rats. Quercetin totally or partially prevents these effects caused by Cd. Total thiols (T-SHs), reduced glutathione (GSH), and reductase glutathione (GR) activities decreased and glutathione S-transferase (GST) activity increased in Cd exposed rats. Co-treatment with quercetin prevented reduction in T-SH, GSH, and GR activities and the rise of GST activity. The present findings show that quercetin prevents alterations in oxidative stress parameters as well as AChE and Na + ,K + -ATPase activities, consequently preventing memory impairment and anxiogenic-like behavior displayed by Cd exposure. These results may contribute to a better understanding of the neuroprotective role of quercetin, emphasizing the influence of this flavonoid in the diet for human health, possibly preventing brain injury associated with Cd intoxication.
Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and anti... more Oxidative stress is characterized by imbalanced reactive oxygen species (ROS) production and antioxidant defenses. Two main antioxidant systems exist. The nonenzymatic system relies on molecules to directly quench ROS and the enzymatic system is composed of specific enzymes that detoxify ROS. Among the latter, the superoxide dismutase (SOD) family is important in oxidative stress modulation. Of these, manganese-dependent SOD (MnSOD) plays a major role due to its mitochondrial location, i.e., the main site of superoxide (O 2 •À ) production. As such, extensive research has Advances in Clinical Chemistry, Volume 68 # 2015 Elsevier Inc.
Revista Brasileira de Geriatria e Gerontologia, 2011
Methods -We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veran... more Methods -We analyzed 70 elderly patients aged 80 years or more who were part of the Projeto Veranópolis. We used the gene amplification technique through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and cleavage with the restriction enzyme Hha I to identify the ApoE genotypes. The most frequent genotypes were compared considering biological variables and cardiovascular risks and morbidity.
Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there a... more Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there are growing numbers of smokers who continue to smoke at a low daily rate, or less frequently (non-daily smokers). This group needs to be better characterized in order to direct preventive actions and public health policies. The aim here was to compare lifestyle, health characteristics and alcoholism problems among young adult smokers, non-daily smokers and non-smokers. This was a cross-sectional study in which volunteers from the university community and its surrounds in Santa Maria, State of Rio Grande do Sul, Brazil, were included between October 2007 and January 2008. Out of 1240 volunteers initially contacted in a university cafeteria, a total of 728 participants of mean age 22.45 ± 3.32 years were selected for final analysis. Data were collected using structured questionnaires. In general, it was observed that the non-daily smokers showed intermediate characteristics in relation to the smokers and non-smokers. However, there was a significant association between non-daily smoking and alcohol abuse. The non-daily smokers presented an odds ratio of 2.4 (95% confidence interval: 1.10-5.48) in relation to the daily smokers and an odds ratio of 3.3 (confidence interval: 1.7-6.5) in relation to the non-smokers, with regard to presenting a positive CAGE test, thereby indicating alcohol abuse or dependence. The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.
The aim of the present study was to evaluate the associations of metabolic disorders and anthropo... more 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. a Agricultural and fishing activities; comparison between categorical variables were performed by Chi-square statistical test.
Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of micr... more Several compounds present in fruits as polyphenols are able to kill or inhibit the growth of microorganisms. These proprieties are relevant mainly in tropical areas, as Amazonian region where infectious are highly prevalent. Therefore, this study investigated the antimicrobial activity of tucumã Amazonian fruit against 37 microorganisms. The potential role of oxidative metabolism imbalance was also studied as causal mechanism of antimicrobial activity. The results showed antibacterial effect of pulp and peel tucumã hydro-alcoholic extracts on three Gram-positive bacteria (Enterococcus faecalis, Bacillus cereus, Listeria monocytogenes) and antifungal effect against Candida albicans. The antimicrobial contribution of main chemical compounds (quercetin, rutin, β-carotene and gallic, caffeic and chlorogenic acids) found in tucumã extracts was also investigated showing an inhibitory effect depending of the organism mainly by quercetin in bacteria and rutin in C. albicans. Analysis of kinetic of DNA releasing in extracellular medium by fluorescence using DNA Pico Green assay(®) and reactive oxygen species production (ROS) showed potential oxidative imbalance contribution on tucumã inhibitory effect. In B. cereus and C. albicans this effect was clear since after 24h the ROS levels were higher when compared to negative control group. In conclusion, tucumã extracts present antimicrobial activity to four microorganisms that have large problems of drug resistance, and the possible mechanism of action of this Amazon fruit is related to REDOX imbalance.
Background: Previous experimental investigations have suggested that guaraná (Paullinia cupana Ku... more Background: Previous experimental investigations have suggested that guaraná (Paullinia cupana Kunth, supplied by EMBRAPA Oriental) consumption is associated with a lower prevalence of cardiovascular metabolic diseases and has positive effects on lipid metabolism, mainly related to low density lipoprotein (LDL) levels. As LDL oxidation is an important initial event in the development of atherosclerosis, we performed in vitro and in vivo studies to observe the potential effects of guaraná on LDL and serum oxidation. Methods: The in vivo protocol was performed using blood samples from 42 healthy elderly subjects who habitually ingested guaraná (GI) or never ingested guaraná (NG). The formation of conjugated dienes (CDs) was analyzed from serum samples. The in vitro protocols were performed using LDL obtained from 3 healthy, non-fasted, normolipidemic voluntary donors who did not habitually ingest guaraná in their diets. The LDL samples were exposed to 5 different guaraná concentrations (0.05, 0.1, 0.5, 1, and 5 μg/mL).
Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Gran... more Schinus lentiscifolius Marchand (syn. Schinus weinmannifolius Engl) is a plant native to Rio Grande do Sul (Southern Brazil) and has been used in Brazilian traditional medicine as antiseptic and antimicrobial for the treatment of many different health problems as well as to treat leucorrhea and to assist in ulcer and wound healing. Although it is a plant widely used by the population, there are no studies proving this popular use. The crude aqueous extract, the crude neutral methanol extract, fractions prepared from this extract (n-hexane, ethyl acetate, and n-butanol), pure compounds isolated from these fractions, and derivatives were investigated in vitro for antimicrobial activities against five Gram positive bacteria: Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, three Gram negative bacteria: Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei, and four yeasts: Candida albicans, Candida tropicalis, Cryptococcus neoformans, and Saccharomyces cerevisiae. The isolated compound moronic acid, which is the most active, was tested against a range of other bacteria such as two Gram positive bacteria, namely, Bacillus cereus, Enterococcus spp, and six Gram negative bacteria, namely, Burkholderia cepacia, Providencia stuartii, Morganella morganii, Enterobacter cloacae, Enterobacter aerogenes, and Proteus mirabilis. The leaf aqueous extract (decoction) of Schinus lentiscifolius showed a broad spectrum of antibacterial activity, ranging from 125 to 250 μg/ml (MIC) against the tested bacteria and fungi. The n-hexane extract, despite being very little active against bacteria, showed an excellent antifungal activity, especially against Candida albicans (MIC=25 μg/ml), Candida tropicalis (MIC=15.5 μg/ml), and Cryptococcus neoformans, (MIC=15.5 μg/ml). From the acetate fraction (the most active against bacteria), compounds 1-6 were isolated: nonadecanol (1), moronic acid (2), gallic acid methyl ester (3), gallic acid (4), quercetin (5) and quercitrin (6). The minimal inhibitory concentration (MIC) of moronic acid between 1.5 and 3 μg/ml against most of the tested bacteria shows that it is one of the metabolites responsible for the antibacterial activity of Schinus lentiscifolius. The antimicrobial activity and some constituents of Schinus lentiscifolius are reported for the first time. The results of the present study provide scientific basis for the popular use of Schinus lentiscifolius for a number of different health problems.
The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Ma... more The antioxidant effects of the hydro-alcoholic guaraná extract (Paullinia cupana var. sorbilis Mart.) on nitric oxide (NO) and other compounds generated from the degradation of sodium nitroprusside (SNP) in an embryonic fibroblast culture (NIH-3T3 cells) were evaluated. The guaraná bioactive compounds were initially determined by high-performance liquid chromatography: caffeine = 12.240 mg/g, theobromine = 6.733 mg/g and total catechins = 4.336 mg/g. Cells were exposed to 10 lM SNP during a 6 h period because the cells exhibited >90% mortality at this concentration. Guaraná was added to the cultures in five concentrations (0.5, 1, 5, 10 and 20 mg/mL). The guaraná antioxidant effect was evaluated by viability assays, biochemical oxidation [lipid peroxidation, catalase and superoxide dismutase (SOD) activity] and genotoxicity (DNA Comet assay) analysis. Additionally, oxidative stress was evaluated by a 2,7-dihydrodichlorofluorescein diacetate fluorescence assay. Guaraná reverted the SNP toxicity mainly at lower concentrations (<5 mg), which decreased cell mortality, lipid peroxidation, DNA damage and cell oxidative stress as well as increased the SOD levels. These results demonstrate that guaraná has an antioxidant effect on NO metabolism in situations with higher cellular NO levels.
The effect of guaraná on cytokine levels was also evaluated in culture medium supplemented with g... more The effect of guaraná on cytokine levels was also evaluated in culture medium supplemented with glucose and insulin. a randomised, placebo-controlled in vivo assay was also performed to evaluate the potential influence of guaraná on the blood cytokine levels of 14 healthy volunteers supplemented for 14 days. The effect of guaraná was similar to that of resveratrol, a known anti-inflammatory molecule, decreasing Il-1β, Il-10 and Ig-γ levels and increasing Il-10 levels compared to those of the control group. The in vitro insulin supplementation potentiated the effect of guaraná on some cytokines. a decreasing effect on the blood inflammatory cytokine levels, along with an increase in Il-10 levels, was also observed in volunteers supplemented with guaraná. In conclusion, guaraná positively modulates cytokines associated with inflammatory metabolism.
Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative ... more Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O À 2 ). The superoxide dismutase manganese dependent (SOD2) catalyzes O À 2 in H 2 O 2 into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-a, IFN-c). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question.
Objectives: To investigate the association of the + 3953 IL-1B gene polymorphism in healthy subje... more Objectives: To investigate the association of the + 3953 IL-1B gene polymorphism in healthy subjects with serum oxidized LDL (oxLDL) levels.
Uploads
Papers by Ivana Da Cruz