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.

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.

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.