The Protective Effect of Lithium Against Rotenone may be Evolutionarily Conserved: Evidence from Eisenia fetida, a Primitive Animal with a Ganglionic Brain.

Chronic exposure to stress is a non-adaptive situation that is associated with mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS), especially superoxide anion (SA). This accumulation of ROS produces damage-associated molecular patterns (DAMPs), which activate chronic inflammatory states and behavioral changes found in several mood disorders. In a previous study, we observed that an imbalance of SA triggered by rotenone (Ro) exposure caused evolutionarily conserved oxi-inflammatory disturbances and behavioral changes in Eisenia fetida earthworms. These results supported our hypothesis that SA imbalance triggered by Ro exposure could be attenuated by lithium carbonate (LC), which has anti-inflammatory properties. The initial protocol exposed earthworms to Ro (30 nM) and four different LC concentrations. LC at a concentration of 12.85 mg/L decreased SA and nitric oxide (NO) levels and was chosen to perform complementary assays: (1) neuromuscular damage evaluated by optical and scanning electron microscopy (SEM), (2) innate immune inefficiency by analysis of Eisenia spp. extracellular neutrophil traps (eNETs), and (3) behavioral changes. Gene expression was also evaluated involving mitochondrial (COII, ND1), inflammatory (EaTLR, AMP), and neuronal transmission (nAchR α5). LC attenuated the high melanized deposits in the circular musculature, fiber disarrangement, destruction of secretory glands, immune inefficiency, and impulsive behavior pattern triggered by Ro exposure. However, the effects of LC and Ro on gene expression were more heterogeneous. In summary, SA imbalance, potentially associated with mitochondrial dysfunction, appears to be an evolutionary component triggering oxidative, inflammatory, and behavioral changes observed in psychiatric disorders that are inhibited by LC exposure.

A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.

In Vitro Biological Properties of Solanum sessiliflorum (Dunal), an Amazonian Fruit.

Solanum sessiliflorum is an Amazonian fruit (cubiu) that has been domesticated since pre-Colombian era. It is also used in folk medicine to treat some clinical conditions. This investigation chemically characterized and analyzed the in vitro antioxidant and antitumoral effect of a cubiu pulp/seed hydroalcoholic extract. Cubiu extract was chemically characterized by high-performance liquid chromatography with diode array detector (HPLC-DAD), its antioxidant capacity measured by 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the following complementary in vitro protocols were performed: (1) cytoprotective effect of cubiu on human peripheral blood mononuclear cells (PBMCs) exposed to H2O2, a genotoxic and procarcinogen molecule; (2) effect of cubiu on low density lipoproteins oxidation; and (3) cytotoxic and antiproliferative effect on breast (MCF-7) and colorectal (HT-29) cancer cell lines. Biochemical and flow cytometry analyses were conducted in these protocols. Cubiu extract presented high concentrations of caffeic and gallic acids, beta-carotene, catechin, quercetin, and rutin, and its antioxidant capacity was confirmed. Cubiu attenuated H2O2 cytotoxicity on PBMCs, presented lowering effect on LDL oxidation, and induced mortality and proliferative inhibition of colorectal cancer cells. In cancer cells, cubiu extract at 10 µg/mL showed similar effects to 5-fluorouracil chemo drug reducing its viability and frequency of S-phase, indicating that cells are undergoing mitosis. In summary, despite the limitations of in vitro protocols, our results suggest that cubiu has several biological properties that affect human health.

Interaction between low-level laser therapy and Guarana (Paullinia cupana) extract induces antioxidant, anti-inflammatory, and anti-apoptotic effects and promotes proliferation in dermal fibroblasts.

BACKGROUND: Low-level laser therapy (LLLT) has several clinical applications; however, its benefits are not universal. Therefore, combination therapy with LLLT and extracts from the guarana (Paullinia cupana) plant may improve its effectiveness as guarana extracts exhibit anti-aging properties. OBJECTIVES: To evaluate the antioxidant, anti-inflammatory, anti-apoptotic, and proliferative effects of combined LLLT and guarana extract therapy on human dermal fibroblasts. METHODS: Human dermal fibroblasts (HFF-1) were cultured and initially exposed to several concentrations (1, 3, 5, 10, 30 µg/mL) of guarana extract. The experimental concentration of guarana extract was selected by analyzing cytokine levels, DNA oxidation, and apoptotic markers in LLLT-exposed (4 J/cm2 ) and LLLT-unexposed fibroblast cultures. After 72 hours, the cells were analyzed using spectrophotometric, fluorimetric, immunological, and gene expression (qRT-PCR) assays. Flow cytometry was used to evaluate the effect of each treatment on cell cycle. RESULTS: Fibroblasts treated with guarana (5 µg/mL) exhibited anti-inflammatory and anti-apoptotic properties been used in complementary protocols. Combined guarana and LLLT treatment significantly decreased protein carbonylation, lipoperoxidation, and DNA oxidation, downregulated the mRNA and protein expression of pro-inflammatory molecules, and upregulated IL-10 gene and protein expression. Guarana plus LLLT also decreased the levels of caspases 1, 3, and 8, increased the percentage of S-phase cells, and decreased FGF-1 and KGF-1 levels. Some of these changes were also observed after treatment with guarana or LLLT alone. CONCLUSIONS: Our results suggest that concomitant treatment with guarana and LLLT may promote fibroblast biostimulation and thus is clinically relevant.

In vitro effect of low-level laser therapy on the proliferative, apoptosis modulation, and oxi-inflammatory markers of premature-senescent hydrogen peroxide-induced dermal fibroblasts.

Skin aging is a complex biological process induced by intrinsic and extrinsic factors which is characterized by clinical and cellular changes, especially dermal fibroblasts. It is possible that, some procedures, such as low-level laser therapy (LLLT), could decelerate this process. To test this hypothesis, this study evaluated the in vitro LLLT on dermal fibroblast cell line (HFF-1) with premature senescence H2O2-induced. HFF-1 cells were cultured in standardized conditions, and initially H2O2 exposed at different concentrations. Fibroblasts were also just exposed at different LLLT (660 nm) doses. From these curves, the lowest H2O2 concentration that induced indicators of premature senescence and the lowest LLLT doses that triggered fibroblast proliferation were used in all assays. Cellular mortality, proliferation, and the levels of oxidative, inflammatory cytokines, apoptotic markers, and of two growth signaling molecules (FGF-1 and KGF) were compared among treatments. The H2O2 at 50 µM concentration induced some fibroblast senescence markers and for LLLT, the best dose for treatment was 4 J (p < 0.001). The interaction between H2O2 at 50 µM and LLLT at 4 J showed partially reversion of the higher levels of DNA oxidation, CASP 3, CASP 8, IL-1B, IL-6, and INFy induced by H2O2 exposure. LLLT also trigger increase of IL-10 anti-inflammatory cytokine, FGF-1 and KGF levels. Cellular proliferation was also improved when fibroblasts treated with H2O2 were exposed to LLLT (p < 0.001). These results suggest that in fibroblast with some senescence characteristics H2O2-induced, the LLLT presented an important protective and proliferative action, reverting partially or totally negative effects triggering by H2O2.

The Influence of a Xanthine-Catechin Chemical Matrix on in vitro Macrophage-Activation Triggered by Antipsychotic Ziprasidone.

Ziprasidone (ZIP) is an effective antipsychotic with low side effects than other second-generation antipsychotics. Despite this, there are reports of adverse events and previous studies associating the use of ZIP the inflammatory response. It is possible to infer that bioactive molecules present in some foods could attenuate peripheral inflammatory and oxidative stress potentially triggered ZIP. This is the case of guaraná xanthine-catechin chemical matrix (XC-Mix) that presents caffeine, theobromine, and catechin. The in vitro protocols using murine RAW 264.7 cell macrophages were ZIP-exposure in culture medium supplemented with chemical isolated and admixture of Caf, The, and Cat. Main results showed that supplementation with isolated and XC-mix had a lowering effect on 72 h macrophages proliferation. XC-mix with 1:1:1 proportion at 25 µg/mL of each caffeine, theobromine, and catechin, molecules present lowering effect on nitric oxide levels, oxidative stress markers (DNA oxidation quantified by 8-hydroxy-2' -deoxyguanosine), lipoperoxidation, and protein carbonylation. XC-mix also decreased protein levels and downregulated genes of proinflammatory cytokines (IL-1ß, IL-6, TNF-α). At contrary, XC-Mix increased levels and upregulated gene of anti-inflammatory IL-10 cytokine. The results suggest that XC-matrix could present some beneficial action on peripheral proinflammatory effects ZIP-triggered. Complementary in vivo studies could be useful to confirm these in vitro findings described here.

Superoxide-hydrogen peroxide genetic imbalance modulates differentially the oxidative metabolism on human peripheral blood mononuclear cells exposed to seleno-L-methionine.

Superoxide-hydrogen peroxide (S-HP) imbalance genetically caused by a gene polymorphism in the human manganese superoxide dismutase enzyme (Val16Ala-MnSOD) is associated with several diseases. Into mitochondria, MnSOD catalyses superoxide radical producing HP and oxygen. Ala-MnSOD genotype presents a high MnSOD efficiency and generates the highest HP concentrations that has been associated with the risk of several cancer types. Cellular selenoenzymes glutathione peroxidase and thioredoxin reductase (TrxR) and catalase (CAT) are essential to HP removal produced in excess in cells. Since, synthesis and activities of selenoenzymes are selenium dependent, we hypothesized that AA-MnSOD cells could have an improvement on antioxidant status undergoing Seleno-L-methionine (SeMet) treatment. This study performed an in vitro protocol to evaluate the response of peripheral blood mononuclear cells (PBMC) carriers of different Val16Ala-MnSOD genotypes exposed to SeMet. SeMet effects on cell viability, apoptosis induction and modulation of oxidative variables were determined using spectrophotometric, flow cytometry, fluorimetric and immunoassays. Gene modulation of antioxidant enzymes was also performed by qRT-PCR. From an initial protocol using heterozygous (AV) cells was determined that 1nM SeMet presented a cytoprotective effect. However, whereas this concentration did not change AA viability, in VV cells it was cytotoxic by increasing necrosis events. SeMet induced higher selenoenzymes levels in AA and VV cells and decreased oxidative markers levels including DNA damage. The results suggest a pharmacogenetic positive response of SeMet effect on AA-cells. Future studies in vivo could be essential to evaluate the potential clinical impact of S-HP imbalance after use of foods or supplements containing SeMet.