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Vasconcellos M.C.,Federal University of Amazonas | Bezerra D.P.,Federal University of Sergipe | Fonseca A.M.,Federal University of Ceara | Lemos T.L.G.,Federal University of Ceara | And 2 more authors.
Melanoma Research | Year: 2011

Biflorin, an ortho-naphthoquinone, is an active compound found in the roots of Capraria biflora L. It has been reported that biflorin presents anticancer activity, inhibiting both tumor cell line growth in culture and tumor development in mice. The aim of this study was to examine the effectiveness of biflorin treatment using both in-vitro and in-vivo melanoma models. Biflorin displayed considerable cytotoxicity against all tested cell lines, with half maximal inhibitory concentration values ranging from 0.58 μg/ml in NCI H23 (human lung adenocarcinoma) to 14.61 μg/ml in MDA-MB-231 (human breast cancer) cell lines. In a second set of experiments using B16 melanoma cells as a model, biflorin reduced cell viability but did not cause significant increase in the number of nonviable cells. In addition, the DNA synthesis was significantly inhibited. Flow cytometry analysis showed that biflorin may lead to an apoptotic death in melanoma cells, inducing DNA fragmentation and mitochondria depolarization, without affecting membrane integrity. In B16 melanoma-bearing mice, administration of biflorin (25mg/day) for 10 days inhibited tumor growth, and also increased the mean survival rate from 33.3±0.9 days (control) to 44.5±3.4 days (treated). Our findings suggest that biflorin may be considered as a promising lead compound for designing new drugs to be used in the treatment of melanoma. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Danesi C.C.,Lutheran University of Brazil | Danesi C.C.,Federal University of Santa Maria | Bellagamba B.C.,Lutheran University of Brazil | Dihl R.R.,Lutheran University of Brazil | And 5 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2010

Recent studies have added paclitaxel (PAC) to traditional cisplatin (CIS) regimen to treat squamous cell carcinoma of the head and neck. The target of these antineoplastic agents is nuclear DNA for CIS and microtubules for PAC, although it is not restricted to malignant cells. In this study, the genotoxicity of the combined treatment of PAC and CIS was investigated using the standard version of the wing Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. Quantitative and qualitative genotoxic effects of these compounds were estimated by comparing wing spot frequencies in marker-heterozygous to balancer-heterozygous flies. Two different concentrations of PAC (0.0025 and 0.005 mM) and CIS (0.025 and 0.05 mM) as well as combinations of them were employed. The results demonstrated that the spindle poison PAC alone was not genotoxic in this test system, while CIS was able to induce a high incidence of DNA damage in both genotypes, mainly related to somatic recombination. The data obtained for the combined treatments showed that its genotoxicity varied with the concentrations used. In small concentrations the number of total spots induced by combination was reduced in relation to CIS 0.025 mM just for marker-heterozygous flies, showing that somatic recombination was the prevalent event involved. At higher concentrations the combined treatment showed significant reductions in the frequencies of large single spots, for both genotypes, and twin spots for marker-heterozygous flies, but did not significantly reduce the total spots frequency in either genotype. The data suggest that aneugenic activity of PAC could be responsible for the reduction in the genotoxicity of CIS. © 2010 Elsevier B.V. All rights reserved.

Ferreira J.L.R.,Grande Rio University | Ferreira J.L.R.,Institute Ciencias Biologicas ICB | Ferreira J.L.R.,Brazilian National Council for Scientific and Technological Development | Lonne M.N.,University of Buenos Aires | And 10 more authors.
Aquatic Toxicology | Year: 2014

Compounds from the nanotechnology industry, such as carbon-based nanomaterials, are strong candidates to contaminate aquatic environments because their production and disposal have exponentially grown in a few years. Previous evidence shows that fullerene C60, a carbon nanomaterial, can facilitate the intake of metals or PAHs both in vivo and in vitro, potentially amplifying the deleterious effects of these toxicants in organisms. The present work aimed to investigate the effects of fullerene C60 in a Danio rerio (zebrafish) hepatocyte cell lineage exposed to benzo[a]pyrene (BaP) in terms of cell viability, oxidative stress parameters and BaP intracellular accumulation. Additionally, a computational docking was performed to investigate the interaction of the fullerene C60 molecule with the detoxificatory and antioxidant enzyme πGST. Fullerene C60 provoked a significant (p<0.05) loss in cellular viability when co-exposed with BaP at 0.01, 0.1 and 1.0μg/L, and induced an increase (p<0.05) in BaP accumulation in the cells after 3 and 4h of exposure. The levels of reactive oxygen species (ROS) in the cells exposed to BaP were diminished (p<0.05) by the fullerene addition, and the increase of the GST activity observed in the BaP-only treated cells was reduced to the basal levels by co-exposure to fullerene. However, despite the potential of the fullerene molecule to inhibit π GST activity, demonstrated by the computational docking, the nanomaterial did not significantly (p>0.05) alter the enzyme activity when added to GST purified extracts from the zebrafish hepatocyte cells. These results show that fullerene C60 can increase the intake of BaP into the cells, decreasing cell viability and impairing the detoxificatory response by phase II enzymes, such as GST, and this latter effect should be occurring at the transcriptional level. © 2013 Elsevier B.V.

Silva B.C.,Federal University of Minas Gerais | De Miranda A.S.,Fundacao Oswaldo Cruz | De Miranda A.S.,Federal University of Minas Gerais | Rodrigues F.G.,Fundacao Oswaldo Cruz | And 9 more authors.
Current Neurovascular Research | Year: 2015

Stroke is one of the most frequent causes of death and disability worldwide causing a major clinical and socioeconomic impact. Although the pathophysiology of brain ischemia and reperfusion is complex, the inflammatory process plays an important role in pathogenesis, contributing to the expansion of brain injury. The 5-lipoxygenase (5-LOX) is a key enzyme in the biosynthesis of the leukotrienes and has been implicated and in the central nervous system (CNS) disorders such as Alzheimer's disease and acute ischemic stroke. Zileuton, a selective 5-LOX inhibitor, has antiinflammatory properties and exerts an inhibitory effect on inflammatory diseases. The objective of this study was to evaluate the effects of blocking 5-LOX activity in a murine model of transient and global brain ischemia. Zileuton improved neurological deficits and significantly decrease volume and density of lesion, compared to vehicle-ischemic animals measured by magnetic resonance imaging (MRI). In addition, the blockage of 5-LOX reduced infarct area and histopathological changes. Furthermore, by enzyme immunoassay (ELISA) increased brain levels of tumor necrosis factor-alpha (TNFalpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-C motif) ligand 3 (CCL3) and chemokine (C-C motif) ligand 5 (CCL5) were detected in the vehicle-ischemic group, whereas in Zileuton-ischemic group presented reduction of these mediators. The concentration of the antiinflammatory cytokine interleukin-10 (IL-10) was increased after 5-LOX inhibition. Our results suggest that Zileuton decreases brain damage and reduces inflammatory cytokines expression in the CNS which contributes, at least in part, to improve the neurological outcome of brain ischemia. © 2015 Bentham Science Publishers.

Kutter M.T.,Grande Rio University | Monserrat J.M.,Grande Rio University | Monserrat J.M.,Institute Ciencias Biologicas ICB | Tesser M.B.,Grande Rio University | Tesser M.B.,Institute Oceanografia IO
Aquaculture | Year: 2012

This study evaluated the effect of four doses of α-lipoic acid (LA) from dietary supplementation on growth performance, body composition and anti-oxidant status in the fish Trachinotus marginatus. The fish fed for 42days with a diet containing different concentrations of LA: 0mgLAkg -1 dry food, 316.4mgLAkg -1 dry food, 524mgLAkg -1 dry food, 890.4mgLAkg -1 dry food and 1367.3mgLAkg -1 dry food. High doses (890.4 and 1367.3mgLAkg -1) of dietary LA significantly reduced the growth (p<0.05), the specific growth rate and the protein efficiency ratio. When administered in high doses of LA, supplementation significantly decreased the feed intake (p<0.05), although the feed conversion ratio increased (p<0.05) in these groups. The carcass composition exhibited the highest lipid values in the control group and in the fish exposed to 316.4 and 524mgLAkg -1 dry food (p<0.05). The LA dietary supplementation increased the brain activity of glutathione-S-transferase (GST) when administered at a dose of 890.4mgLAkg -1 dry food, and the lipid peroxidation in muscle was reduced (at all LA doses) (p<0.05). The results obtained regarding growth, antioxidant status and lipid and protein metabolism indicated that LA could be supplemented in diets for T. marginatus at doses between 316.4 and 524mgLAkg -1 dry food. © 2012 Elsevier B.V.

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