Guarana improves behavior and inflammatory alterations triggered by methylmercury exposure: an in vivo fruit fly and in vitro neural cells study.

Methylmercury (MeHg) is a well-known environmental pollutant associated with neurological and developmental deficits in animals and humans. However, epidemiological data showed that people living in the Amazon region although exposed to MeHg do not present these effects probably due to the protective effect of certain foods. We hypothesized here if guarana, a highly caffeinated fruit and consumed on a daily basis by Amazon people, could have some protective effect against MeHg toxicity using two complementary approaches. To assess locomotor impairment and sleep disruption, we used fruit fly (Drosophila melanogaster) model, and to evaluate neuroinflammation, we used human SH-SY5Y neural cells by measuring inflammatory cytokines levels. Results showed that guarana had a protective effect on the locomotor activity of male fruit flies reducing the excessive sleepiness caused by MeHg and increasing daily activity. Also, guarana increased the viability of flies and attenuated neural cells mortality. In addition, guarana reduced all pro-inflammatory cytokines levels increased by MeHg, along with caspase-1, caspase -3, caspase-8, and 8-dOHG levels, whereas increased the anti-inflammatory (IL-10) cytokine levels, which was decreased by MeHg. Our study provides new insights on the protective effects of guarana on the viability, locomotor activity, sleep, and activity patterns in vivo and the in vitro neuronal anti-inflammatory effect against MeHg toxicity.

Impact of Lipid-Inflammatory-Oxidative Metabolism on Auditory Skills after Hearing Aid Fitting in the Elderly.

This study aimed to assess whether lipid-inflammatory-oxidative metabolism influences auditory processing skills, and whether they function in changing auditory performance after hearing aid fitting in the elderly. Twelve subjects with bilateral hearing loss were submitted to blood tests (to check their lipid-inflammatory-oxidative metabolism) and auditory processing skill tests. After 3 months of using the hearing aids, their auditory skills were re-evaluated and the data were correlated statistically. Oxidative stress levels mainly showed some impact on auditory temporal processing; such a relation and others should best be examined in further studies with larger populations.

Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs.

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.

Antimicrobial activity of Amazon Astrocaryum aculeatum extracts and its association to oxidative metabolism.

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, ß-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.

Association between Machado-Joseph disease and oxidative stress biomarkers.

Spinocerebellar ataxia type 3, also called Machado-Joseph disease (MJD), is an hereditary autosomal dominant neurodegenerative disease that affects the cerebellum and its afferent and efferent connections. Since the mechanism by which mutant ataxin-3 eventually leads to neuronal death is poorly understood, additional investigations to clarify the biological alterations related to Machado-Joseph disease are necessary. Recent investigations suggest that oxidative stress may contribute significantly to Machado-Joseph disease. We compared markers of oxidative stress between Machado-Joseph disease and healthy control subjects. The results showed that Machado-Joseph patients have higher catalase levels and lower thiol protein levels compared to control subjects. The peripheral blood lymphocyes of MJD patients also showed higher levels of DNA damage by the comet assay than control subjects. Our results corroborate the hypothesis that the oxidative stress is associated with MJD patients. However, whether strategies to increase cellular antioxidative capacity may be effective therapies for the treatment of Machado-Joseph disease is an open question.

Inflammatory cytokines in vitro production are associated with Ala16Val superoxide dismutase gene polymorphism of peripheral blood mononuclear cells.

Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(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-α, IFN-γ). 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.

Effect of the interleukin-1B gene on serum oxidized low-density lipoprotein levels.

OBJECTIVES: To investigate the association of the +3953 IL-1B gene polymorphism in healthy subjects with serum oxidized LDL (oxLDL) levels. DESIGN AND METHODS: We selected 255 subjects who were non-smokers and who had no cardiovascular or other chronic degenerative diseases, and we measured the oxLDL and other glucose levels, lipid biomarkers and biological variables that are related to cardiovascular metabolism. The +3953 IL-1B gene polymorphism was determined using molecular genetics techniques (PCR-RFLP). RESULTS: A significant association among the +3953 IL-1B genotypes and the oxLDL level was observed. The TT genotype presented lower oxLDL levels than the other genotypes. A multivariate analysis showed that this result was independent of the sex, age, obesity and hypertension status of the subjects. CONCLUSIONS: Our results suggest that the IL-1B gene polymorphism affects the modulation of serum oxLDL levels.

Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene citrate in oxidative metabolism.

This study investigated the in-vitro antioxidant properties of the ovulation induction drug, clomiphene citrate, and assessed whether its effects are influenced by the Val16Ala polymorphism in the SOD2 gene, which encodes manganese superoxide dismutase enzyme. The investigation involved an in-vitro experimental protocol testing the effect of different concentrations of clomiphene citrate on antioxidant capacity, reactive oxygen species (ROS) production and peripheral blood mononuclear cell (PBMC) culture viability. A total of 58 healthy adult women were genotyped for the Val16Ala SOD2 polymorphism, and blood samples were collected to perform in-vitro experiments. ROS production and cytotoxicity assays were performed on blood and PBMC from carriers of different Val16Ala SOD2 genotypes. Clomiphene citrate exhibited antioxidant capacity and effects and decreased ROS production. The AA genotype displayed a more responsive antioxidant effect with clomiphene citrate treatment than other genotypes. AA and AV PBMC showed an increase in viability following treatment with 10 µmol/l clomiphene citrate when compared with control groups. The results suggest that clomiphene citrate exhibits antioxidant activity similar to that observed with other selective oestrogen receptor modulators, and the intensity of the effect appears to be SOD2 polymorphism dependent. This study was performed to investigate whether clomiphene citrate, a drug broadly used to evaluate reproductive function in women, presents antioxidant effects and if these effects could be influenced by genetic variation in the women. We found evidence that clomiphene citrate has some antioxidant properties similar to those observed with other selective oestrogen receptor modulators such as tamoxifen. As the antioxidant enzyme manganese superoxide dismutase (SOD2) is considered a key molecule involved in female reproductive metabolism, we also tested if a functional SOD2 gene polymorphism (Val16Ala) could influence the in-vitro antioxidant clomiphene citrate response. Significant differences of the clomiphene citrate antioxidant effect on PBMC with different Val16Ala SOD genotypes were observed in this study. Based on these results, we could speculate that alterations in SOD2 activity caused by the Val16Ala polymorphism can result in differential responses to drugs such as clomiphene citrate. In assisted reproduction clinics, clomiphene citrate is commonly used to induce ovulation, especially in patients with polycystic ovary syndrome. However, some women have clomiphene citrate resistance and either ovulation is not triggered by the drug or ovulation is induced but the pregnancy still fails. The causes of no effect of clomiphene citrate remain unclear and we cannot discard the influence of genetic effects including the Val16Ala SOD2 polymorphism. Therefore, it is important to perform complementary investigations considering the potential pharmacogenetic influence of Val16Ala SOD2 polymorphism on the treatment of polycystic ovary syndrome or in ovulation to elucidate this question.

Lifestyle, health characteristics and alcohol abuse in young adults who are non-daily smokers / Estilo de vida, características de saúde e consumo excessivo de álcool em adultos jovens que são fumantes esporádicos

CONTEXT AND OBJECTIVES: 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. DESIGN AND SETTING: 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. METHODS: 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. RESULTS: 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 percent 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. CONCLUSION: The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.

CONTEXTO E OBJETIVO: Apesar do declínio na prevalência do tabagismo em diversos países, incluindo o Brasil, existe um número crescente de fumantes que continua a fumar em baixa quantidade diária ou com menor frequência (fumantes esporádicos). Esse grupo precisa ser mais bem caracterizado para que se possa direcionar ações preventivas e políticas de saúde pública. O objetivo foi comparar o estilo de vida, características de saúde e problemas de alcoolismo entre fumantes, fumantes esporádicos e não fumantes entre adultos jovens. TIPO DE ESTUDO E LOCAL: Estudo transversal em que se incluíram voluntários da comunidade universitária e do seu entorno entre outubro de 2007 a janeiro de 2008 em Santa Maria, Rio Grande do Sul, Brasil. MÉTODOS: A partir de um contato inicial com 1.240 voluntários numa cafeteria universitária, 728 participantes com idade média de 22.45 ± 3.32 anos foram selecionados para análise final. Os dados foram coletados através de um questionário estruturado. RESULTADOS: Em geral, foi observado que os fumantes esporádicos apresentaram características intermediárias em relação aos fumantes e não fumantes. Entretanto, foi encontrada uma associação significativa entre fumo esporádico e abuso de álcool. Os fumantes esporádicos apresentaram uma razão de chance de 2,4 vezes (intervalo de confiança de 1,10-5,48) em relação aos fumantes diários e uma razão de chance de 3,3 (intervalo de confiança de 1,7-6,5) em relação aos não fumantes de apresentar um teste CAGE positivo indicador de abuso ou dependência de álcool. CONCLUSÃO: O estudo sugere que o tabagismo esporádico e o consumo de álcool são comportamentos concomitantes.

Lifestyle, health characteristics and alcohol abuse in young adults who are non-daily smokers.

CONTEXT AND OBJECTIVES: 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. DESIGN AND SETTING: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.

Association between manganese superoxide dismutase (MnSOD) gene polymorphism and elderly obesity.

Evidence suggests an association between obesity and oxidative stress caused by superoxide production. Since the dismutation of superoxide is catalyzed by superoxide dismutase enzymes, we tested the association between obesity and Ala16Val manganese-dependent superoxide dismutase gene (MnSOD) polymorphism. We analyzed 815 free-living community subjects (> or =60 years old) grouped into subjects who were either obese (BMI > or = 30 kg/m(2)) or non-obese (BMI < 25 kg/m(2)). Additionally, we investigated the possible interaction between the Ala16Val MnSOD gene polymorphism and obesity in the modulation of biochemical and nutritional variables. We found a positive association between MnSOD polymorphism and obesity, since higher VV frequency (28.2%) was observed in the obese group (P = 0.002, odds ratio 1.949, 95% CI: 1.223-3.008). This result was independent of sex, age, diabetes, dyslipidemia, hypertension, and metabolic syndrome. A possible biological explanation of the association described here could be a chronic state of superoxide enzyme imbalance present in VV carriers, which could affect differential metabolic pathways contributing to the obese state.