Lusânia Maria Greggi Antunes

University of São Paulo, San Paulo, São Paulo, Brazil

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Publications (89)241.83 Total impact

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    ABSTRACT: The aim of the present study was to evaluate possible effects of endothelial nitric oxide synthase (eNOS) polymorphisms on systolic (SBP) and diastolic blood pressure (DBP) and on nitrite levels in plasma (NitP) in a population coexposed to methylhemoglobin (MeHg) and lead (Pb) in the Amazonian region, Brazil. Plasmatic levels of hemoglobin Hg (HgP) and Pb (PbP) were determined by inductively coupled plasma-mass spectrometry, whereas NitP were quantified by chemiluminescence. Genotyping was performed by conventional and restriction fragment length polymorphism-polymerase chain reaction assay. The population age ranged from 18 to 87 years (mean 40 ± 16), and the distribution between the sexes was homogenous (63 men and 50 women). Mean HgP and PbP were 7.1 ± 6.1 and 1.1 ± 1.1 µg L(-1), respectively. PbP was correlated to SBP and DBP, whereas no effects were observed for HgP on blood pressure. Subjects carrying the 4b allele in intron 4 presented greater SBP and DBP compared with those who had the 4a4a genotype. In addition, interactions between alcohol consumption and the -786 T/C polymorphism were observed on NitP, i.e., individuals carrying the polymorphic allele and drinkers had lower NitP. Taken together, our data give new insights concerning the genetic effects of eNOS polymorphisms on biomarkers related to cardiovascular status in populations coexposed to Hg and Pb.
    Archives of Environmental Contamination and Toxicology 02/2015; DOI:10.1007/s00244-015-0137-8 · 2.01 Impact Factor
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    ABSTRACT: The use of phytochemicals has been widely used as inexpensive approach for prevention of diseases related to oxidative damage due to its antioxidant properties. One of dietary flavonoids is chrysin (CR), found mainly in passion fruit, honey, and propolis. Methylmercury (MeHg) is a toxic metal whose main toxic mechanism is oxidative damage. Thus, the study aimed to evaluate the antioxidant effects of CR against oxidative damage induced by MeHg in Wistar rats. Animals were treated with MeHg (30 µg/kg/bw) in presence and absence of CR (0.10, 1.0, and 10 mg/kg/bw) by gavage for 45 days. Glutathione (GSH) in blood was quantified spectrophotometrically and for monitoring of DNA damage, comet assay was used in leukocytes and hepatocytes. MeHg led to a significant increase in the formation of comets; when the animals were exposed to the metal in the presence of CR, higher concentrations of CR showed protective effects. Moreover, exposure to MeHg decreased the levels of GSH and GSH levels were restored in the animals that received CR plus MeHg. Taken together the findings of the present work indicate that consumption of flavonoids such as CR may protect humans against the adverse health effects caused by MeHg.
    Oxidative Medicine and Cellular Longevity 01/2015; 2015:602360. DOI:10.1155/2015/602360
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    ABSTRACT: Quinoline yellow (QY) is a chinophthalon derivative used in cosmetic compositions for application to the skin, lips, and/or body surface. However, regulatory data about the genotoxicity and/or mutagenicity of this compound are still controversial. Therefore, this work evaluated the genotoxicity of QY using the comet assay and the cytokinesis-block micronucleus cytome assay (CBMN-Cyt) in the metabolically competent cell line HepG2, which closely mimics phase I metabolism. This research also identified the products formed after electrochemical oxidation of the QY dye, which simulates hepatic biotransformation. The primary products generated after the oxidation process were analyzed by High Performance Liquid Chromatography coupled with a Diode Array Detector (HPLC/DAD), which detected the production of 4,4'-diaminodiphenylmethane, 2-methoxy-5-methylaniline and 4,4'-oxydianiline. The results demonstrated that low (from 0.5 to 20μgmL(-1)) QY concentrations were genotoxic in HepG2 cells on both assays and those harmful compounds were detected after the oxidation process. Our findings suggest that this colorant could cause harmful effects to humans if it is metabolized or absorbed through the skin. Copyright © 2014 Elsevier B.V. All rights reserved.
    Mutation Research/Genetic Toxicology and Environmental Mutagenesis 01/2015; 777. DOI:10.1016/j.mrgentox.2014.11.003 · 2.48 Impact Factor
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    ABSTRACT: Venomous and non-venomous snakes possess phospholipase A2 (PLA2) inhibitory proteins (PLIs) in their blood serum. This study shows the expression and biochemical and functional characterization of a recombinant alpha inhibitor from Bothrops alternatus snake, named rBaltMIP. Its expression was performed in Pichia pastoris heterologous system, resulting in an active recombinant protein. The expressed inhibitor was tested regarding its ability to inhibit the phospholipase activity of different PLA2s, showing slight inhibitions especially at the molar ratios of 1:1 and 1:3 (PLA2:PLI). rBaltMIP was also effective in decreasing the myotoxic activity of the tested toxins at molar ratios greater than 1:0.4 (myotoxin:PLI). The inhibition of the myotoxic activity of different Asp49 (BthTX-II and PrTX-III) and Lys49 (BthTX-I and PrTX-I) myotoxins was also performed without the prior incubation of myotoxins/inhibitor in order to analyze the real possibility of using snake plasma inhibitors or recombinant inhibitors as therapeutic agents for treating envenomations. As a result, rBaltMIP was able to significantly inhibit the myotoxicity of Lys49 myotoxins. Histopathological analysis of the gastrocnemius muscles of mice showed that the myotoxins are able to induce severe damage to the muscle fibers of experimental animals by recruiting a large number of leukocyte infiltrates, besides forming an intense accumulation of intercellular fluid, leading to local edema. When those myotoxins were incubated with rBaltMIP, a reduction of the damage site could be observed. Furthermore, the cytotoxic activity of Asp49 PLA2s and Lys49 PLA2-like enzymes on C2C12 cell lines was decreased, as shown by the higher cell viabilities after pre incubation with rBaltMIP. Heterologous expression would enable large-scale obtainment of rBaltMIP, thus allowing further investigations for the elucidation of possible mechanisms of inhibition of snake PLA2s, which have not yet been fully clarified.
    Biochimie 10/2014; 105C. DOI:10.1016/j.biochi.2014.07.001 · 3.14 Impact Factor
  • Toxicology Letters 09/2014; 229:S149. DOI:10.1016/j.toxlet.2014.06.523 · 3.36 Impact Factor
  • Toxicology Letters 09/2014; 229:S231. DOI:10.1016/j.toxlet.2014.06.773 · 3.36 Impact Factor
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    ABSTRACT: Solanum sessiliflorum Dunal is a native shrub often found in the Amazon Forest. Its fruits, known as maná-cubiu, possess an unusual flavor and are consumed in salads and juices, mainly by the local community of Northern Brazil. Because these fruits are used in traditional medicine as hypoglycemic and hypocholesterolemic agents, it is important to establish whether the consumption of maná-cubiu is safe using in vivo genotoxicity tests. Here, we investigated the genotoxic and antigenotoxic potential of maná-cubiu for doxorucibin(DXR)-induced DNA damage using the micronucleus test and the comet assay in Wistar rats. Moreover, oxidative stress parameters were determined in the heart and liver of the animals by measuring the thiobarbituric acid reactive species (TBARS), a biomarker of lipid peroxidation, and reduced glutathione (GSH) content. The relative expression of Pgts2 mRNA in the livers of the animals was also determined. The tests were performed with maná-cubiu pulp (125, 250, 375 or 500 mg/kg body weight - b.w.) by gavage for 14 days, followed by intraperitoneal injection of saline or DXR (16 mg/kg b.w.) immediately after the last gavage, which occurred 24 hours before euthanasia. The results showed that maná-cubiu at all tested doses had no cytotoxic effects on bone marrow cells and was not genotoxic to heart or liver cells. In addition, maná-cubiu treatments decreased DXR-induced DNA damage according to the comet assay in heart and liver cells. Reductions in micronuclei frequency in peripheral blood cells occurred at 125, 250 and 375 mg/kg b.w doses of maná-cubiu, and the TBARS content induced by DXR was also reduced by maná-cubiu. Furthermore, maná-cubiu did not modulate the transcription of the Ptgs2 gene. In conclusion, maná-cubiu pulp fruit was not cytotoxic or genotoxic in Wistar rats, suggesting its safety for human consumption, at least considering genotoxic effects. The antioxidant capacity of maná-cubiu pulp fruit may contribute to the antigenotoxic effects of this fruit at the doses used in this study.
    Food Research International 08/2014; 62. DOI:10.1016/j.foodres.2014.02.036 · 3.05 Impact Factor
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    ABSTRACT: ScopeA compromised nutritional status in methyl-group donors may provoke several molecular alterations triggering the development of nonalcoholic fatty liver disease (NAFLD) in humans and experimental animals. In this study, we investigated a role and the underlying molecular mechanisms of methionine metabolic pathway malfunctions in the pathogenesis of NAFLD.Methods and resultsWe fed female Swiss albino mice a control (methionine-adequate) diet and two experimental (methionine-deficient or methionine-supplemented) diets for 10 weeks, and the levels of one-carbon metabolites, expression of one-carbon and lipid metabolism genes in the livers were evaluated. We demonstrate that both experimental diets increased hepatic levels of S-adenosyl-l-homocysteine and homocysteine, altered expression of one-carbon and lipid metabolism genes, and caused lipid accumulation, especially in mice fed the methionine-deficient diet. Markers of oxidative and ER stress response were also elevated in the livers of mice fed either diet.Conclusion Our findings indicate that both dietary methionine deficiency and methionine supplementation can induce molecular abnormalities in the liver associated with the development of NAFLD, including deregulation in lipid and one-carbon metabolic pathways, and induction of oxidative and ER stress. These pathophysiological events may ultimately lead to lipid accumulation in the livers, triggering the development of NAFLD.
    Molecular Nutrition & Food Research 07/2014; 58(7). DOI:10.1002/mnfr.201300726 · 4.91 Impact Factor
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    ABSTRACT: Lutein (LT) is a carotenoid obtained by diet and despite its antioxidant activity had been biochemically reported, few studies are available concerning its influence on the expression of antioxidant genes. The expression of 84 genes implicated in antioxidant defense was quantified using quantitative reverse transcription polymerase chain reaction array. DNA damage was measured by comet assay and glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) were quantified as biochemical parameters of oxidative stress in mouse kidney and liver. cDDP treatment reduced concentration of GSH and increased TBARS, parameters that were ameliorated in treatment associated with LT. cDDP altered the expression of 32 genes, increasing the expression of GPx2, APC, Nqo1 and CCs. LT changed the expression of 37 genes with an induction of 13 mainly oxygen transporters. In treatments associating cDDP and LT, 30 genes had their expression changed with a increase of the same genes of the cDDP treatment alone. These results suggest that LT might act scavenging reactive species and also inducing the expression of genes related to a better antioxidant response, highlighting the improvement of oxygen transport. This improved redox state of the cell through LT treatment could be related to the antigenotoxic and antioxidant effects observed.
    Food and Chemical Toxicology 05/2014; 70. DOI:10.1016/j.fct.2014.05.018 · 2.61 Impact Factor
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    ABSTRACT: The alkaline version of the single-cell gel (comet) assay is a useful method for quantifying DNA damage. Although some studies on chronic and acute effects of exercise on DNA damage measured by the comet assay have been performed, it is unknown if an aerobic training protocol with intensity, volume, and load clearly defined will improve performance without leading to peripheral blood cell DNA damage. In addition, the effects of overtraining on DNA damage are unknown. Therefore, this study aimed to examine the effects of aerobic training and overtraining on DNA damage in peripheral blood and skeletal muscle cells in Swiss mice. To examine possible changes in these parameters with oxidative stress, we measured reduced glutathione (GSH) levels in total blood, and GSH levels and lipid peroxidation in muscle samples. Performance evaluations (i.e., incremental load and exhaustive tests) showed significant intra and inter-group differences. The overtrained (OTR) group showed a significant increase in the percentage of DNA in the tail compared with the control (C) and trained (TR) groups. GSH levels were significantly lower in the OTR group than in the C and TR groups. The OTR group had significantly higher lipid peroxidation levels compared with the C and TR groups. Aerobic and anaerobic performance parameters can be improved in training at maximal lactate steady state during 8 weeks without leading to DNA damage in peripheral blood and skeletal muscle cells or to oxidative stress in skeletal muscle cells. However, overtraining induced by downhill running training sessions is associated with DNA damage in peripheral blood and skeletal muscle cells, and with oxidative stress in skeletal muscle cells and total blood.
    BMC Physiology 10/2013; 13(1):11. DOI:10.1186/1472-6793-13-11
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    ABSTRACT: Inadequate nutrient intake can influence the genome. Since methionine is an essential amino acid that may influence DNA integrity due to its role in the one-carbon metabolism pathway, we were interested in whether methionine imbalance can lead to genotoxic events. Adult female Swiss mice were fed a control (0.3% DL-methionine), methionine-supplemented (2.0% DL-methionine) or methionine-deficient (0% DL-methionine) diet over a 10-week period. Chromosomal damage was assessed in peripheral blood using a micronucleus test, and DNA damage was assessed in the liver, heart and peripheral blood tissues using a comet assay. The mRNA expression of the mismatch repair genes Mlh1 and Msh2 was analyzed in the liver. The frequency of micronucleus in peripheral blood was increased by 122% in the methionine-supplemented group (p < 0.05). The methioninesupplemented diet did not induce DNA damage in the heart and liver tissues, but it increased DNA damage in the peripheral blood. The methionine-deficient diet reduced basal DNA damage in liver tissue. This reduction was correlated with decreased mRNA expression of Msh2. Our results demonstrate that methionine has a tissue-specific effect because methionine-supplemented diet induced both chromosomal and DNA damage in peripheral blood while the methionine-deficient diet reduced basal DNA damage in the liver.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 09/2013; 62. DOI:10.1016/j.fct.2013.09.004 · 2.99 Impact Factor
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    ABSTRACT: Recent studies have proposed the use of low concentrations of phytochemicals and combinations of phytochemicals in chemoprevention to reduce cytotoxicity and simulate normal ingestion through diet. The purpose of the present study was to evaluate whether the DNA damage, chromosome instability, and oxidative stress induced by cisplatin (cDDP) are modulated by a combination of the natural pigments lutein (LT) and chlorophyll b (CLb). The protective effects observed for synergism between phytochemicals have not been completely investigated. The comet assay and micronucleus test were performed and the catalase activities and glutathione (GSH) concentrations were measured in the peripheral blood, bone marrow, liver, and kidney cells of mice. The comet assay and micronucleus test results revealed that the pigments LT and CLb were not genotoxic or mutagenic and that the pigments presented antigenotoxic and antimutagenic effects in the different cell types evaluated. This protective effect is likely related to antioxidant properties in peripheral blood cells through the prevention of cDDP-induced GSH depletion. Altogether our results show that the combination of LT and CLb, which are both usually present in the same foods, such as leafy green vegetables, can be used safely.
    Human & Experimental Toxicology 08/2013; 32(8):828-836. DOI:10.1177/0960327112468911 · 1.41 Impact Factor
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    ABSTRACT: The chemotherapeutic agent cisplatin (cDDP) is widely used to treat a variety of solid and hematological tumors. However, cDDP exerts severe side effects, such as nephrotoxicity, neurotoxicity, and bone-marrow suppression. The use of some dietary compounds to protect organs that are not targets in association with chemotherapy has been encouraged. This study evaluated the protective effects of chlorophyll b (CLb) on DNA damage induced by cDDP by use of single-cell gel electrophoresis (SCGE) assays. Further, this investigation also determined platinum (Pt) and magnesium (Mg) bioaccumulation in mice tissues after treatment with CLb alone and/or in association of cDDP (simultaneous treatment) by inductively coupled plasma-mass spectroscopy (ICP-MS). All parameters were studied in peripheral blood cells (PBC), kidneys, and liver of mice after administration of CLb (0.2 or 0.5 mg/kg of body weight [b.w.]), cDDP (6 mg/kg b.w.), and the combination CLb 0.2 plus cDDP or CLb 0.5 plus cDDP. Pt accumulation in liver and kidneys was higher than that found in PBC, while DNA damage was higher in kidneys and liver than in PBC. Further, treatment with CLb alone did not induce DNA damage. Evidence indicates that genotoxic effects produced by cDDP may not be related to Pt accumulation and distribution. In combined treatments, CLb decreased DNA damage in tissues, but the PT contents did not change and these treatments also showed that CLb may be an important source of Mg. Thus, our results indicate that consumption of CLb-rich foods may diminish the adverse health effects induced by cDDP exposure. We are grateful to Joana D'Arc Castania Darin and Mara Ribeiro de Almeida (FCFRP-USP) for their technical assistance. The authors would like to thank São Paulo Foundation Research (FAPESP 2005/59552-6, 2008/06793-4, and 2010/05096-8), the National Council of Technological and Scientific Development (CNPq), and Coordination for the Improvement of Higher Level Education Personnel (CAPES) for financial support.
    Journal of Toxicology and Environmental Health Part A 03/2013; 76(6):345-53. DOI:10.1080/15287394.2012.755485 · 1.83 Impact Factor
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    ABSTRACT: Abstract In this study, the ethanolic extract obtained from piquiá pulp was assessed for genotoxicity and oxidative stress by employing the micronucleus test in bone marrow and peripheral blood cells in addition to comet, thiobarbituric-acid-reactive substances (TBARS), and reduced glutathione assays in the liver, kidney, and heart. Additionally, phytochemical analyses were performed to identify and quantify the chemical constituents of the piquiá extract. Wistar rats were treated by gavage with an ethanolic extract from piquiá pulp (75 mg/kg body weight) for 14 days, and 24 h prior to euthanasia, they received an injection of saline or doxorubicin (15 mg/kg body weight, intraperoneally). The results demonstrated that piquiá extract at the tested dose was genotoxic but not mutagenic, and it increased the TBARS levels in the heart. Further studies are required to fully elucidate how the properties of ethanolic extract of piquiá pulp can affect human health.
    Journal of medicinal food 02/2013; DOI:10.1089/jmf.2012.0169 · 1.39 Impact Factor
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    ABSTRACT: Various species of the genus Passiflora have been extensively used in traditional medicine as sedatives, anxiolytics, diuretics and analgesics. In the present study, after the identification and quantification of phytochemical compounds from yellow passion fruit pulp by liquid chromatography-photodiode array-mass spectrometry (HPLC-PDA-MS/MS), its antihypertensive effect was investigated on spontaneously hypertensive rats. Additionally, the renal function, evaluated by kidney/body weight, serum creatinine, proteinuria, urinary flow, reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) and mutagenicity in bone marrow cells were assessed to evaluate the safety of passion fruit consumption. Yellow passion fruit pulp (5, 6 or 8 g/kg b.w.) was administered by gavage once a day for 5 consecutive days. HLPC-PDA-MS/MS analysis revealed that yellow passion fruit pulp contains phenolic compounds, ascorbic acid, carotenoids and flavonoids. The highest dose of passion fruit pulp significantly reduced the systolic blood pressure, increased the GSH levels and decreased TBARS. There were no changes in renal function parameters or the frequency of micronuclei in bone marrow cells. In conclusion, the antihypertensive effect of yellow passion fruit pulp, at least in part, might be due to the enhancement of the antioxidant status. The exact mechanisms responsible by this effect need further investigation. Copyright © 2013 John Wiley & Sons, Ltd.
    Phytotherapy Research 02/2013; DOI:10.1002/ptr.4949 · 2.40 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the neuroprotective effect of a water-soluble formulation of coenzyme Q10 (WS-CoQ10) in PC12 cells exposed to cisplatin, a chemotherapeutic agent with a dose-limiting factor due to neurotoxicity. In the cytokinesis-block micronucleus cytome assay (CBMN Cyt), WS-CoQ10 (at concentrations of 0.1, 0.5 and 1.0μg.mL(-1)) protected PC12 cells from cisplatin-induced DNA damage (0.1μg.mL(-1)), reducing the frequency of micronuclei (MNi) and nuclear buds (NBUDs). WS-CoQ10 did not alter the mRNA expression levels of Tp53 (at a concentration of 1.0μg.mL(-1)) and exhibited neuroprotective activity by stimulating cisplatin-inhibited neurite outgrowth in nerve growth factor (NGF)-differentiated PC12 cells (at a concentration of 0.1μg.mL(-1)). In conclusion, WS-CoQ10 protected the PC12 cells from cisplatin-induced DNA damage and neurotoxicity. Moreover, the neuroprotective effects of WS-CoQ10 suggest a possible application in chemotherapeutic protocols.
    NeuroToxicology 02/2013; DOI:10.1016/j.neuro.2013.02.004 · 3.05 Impact Factor
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    ABSTRACT: In the present study, micronucleus with cytokinesis blocking and comet assays were used to evaluate the genotoxic potential of Bothrops jararacussu, B. atrox, B. moojeni, B. alternatus (Rhinocerophis alternatus) and B. brazili snake venoms, and also of some isolated toxins (MjTX-I, BthTX-I and II myotoxins, BjussuMP-II metalloprotease, and BatxLAAO L-amino acid oxidase) on human lymphocytes. Significant DNA damages were observed, indicating genotoxic potential after exposure of the lymphocytes to the toxins BthTX-I, II and BatxLAAO compared to untreated and cisplatin-treated controls, which were able to induce greater formation of micronuclei. B. brazili, B. jararacussu and B. atrox crude venoms also presented genotoxic potential, and the latter two induced DNA breakage 5 times more often than in normal environmental conditions (control without treatment). B. jararacussu venom and its isolated toxins, as well as an LAAO from B. atrox, were able to cause lymphocyte DNA breakage in the comet test with more than 85% damage levels. The DNA damage evaluation allows a widening of the toxic-pharmacological characterization of snake venoms and their toxins and also contributes to the understanding of the mechanisms of action of these molecules in several human pathologies.
    Toxicon 01/2013; DOI:10.1016/j.toxicon.2012.12.020 · 2.58 Impact Factor
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  • Free Radical Biology and Medicine 11/2012; 53:S82. DOI:10.1016/j.freeradbiomed.2012.10.330 · 5.71 Impact Factor
  • Free Radical Biology and Medicine 11/2012; 53:S82. DOI:10.1016/j.freeradbiomed.2012.10.332 · 5.71 Impact Factor

Publication Stats

1k Citations
241.83 Total Impact Points

Institutions

  • 1998–2015
    • University of São Paulo
      • • Ribeirão Preto School of Pharmaceutical Sciences (FCFRP)
      • • Departamento de Análises Clínicas e Toxicológicas (FBC) (Sao Paulo)
      • • Ribeirão Preto School of Medicine (FMRP)
      • • Departamento de Genética (Ribeirão Preto)
      San Paulo, São Paulo, Brazil
  • 2012
    • University of Alabama at Birmingham
      Birmingham, Alabama, United States
    • CEP America
      Emeryville, California, United States
  • 2009
    • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
      San Paulo, São Paulo, Brazil
  • 2007
    • Universidade Federal do Triangulo Mineiro (UFTM)
      • Departamento de Ciências Biológicas
      Убераба, Minas Gerais, Brazil