Papers by Juliana Mara Serpeloni
Oxidative Medicine and Cellular Longevity, 2015
The use of phytochemicals has been widely used as inexpensive approach for prevention of diseases... more 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 we...
Phytotherapy research : PTR, 2011
The flavonoid quercetin and its derivative rutin were investigated for genotoxicity/antigenotoxic... more The flavonoid quercetin and its derivative rutin were investigated for genotoxicity/antigenotoxicity activity in human hepatoma HepG2 cells using the comet assay. The extract cytotoxicity was evaluated using the trypan blue exclusion dye method with quercetin and rutin concentrations ranging from 0.1 to 200.0 μg/mL of culture medium. Three minor non-cytotoxic concentrations were chosen to evaluate the genotoxicity and antigenotoxicity of the flavonoids (0.1, 1.0 and 5.0 μg/mL) through comet assay. The cultures were treated with three different concentrations of rutin or quercetin (genotoxicity) or their association with Aflatoxin B1 (AFB1), methyl methanesulfonate (MMS) or doxorubicin (DXR) (antigenotoxicity test) in three protocols: pre-treatment, simultaneous treatment and post-treatment. The cell cultures were also treated with 1% DMSO (control group), AFB1, MMS and DXR (positive-control). Statistical analyses were performed using ANOVA and Dunnett's test (p ≤ 0.05). Querceti...
Journal of Toxicology and Environmental Health, Part A, 2013
Human & Experimental Toxicology, 2013
Recent studies have proposed the use of low concentrations of phytochemicals and combinations of ... more 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 ...
Environmental Research, 2011
This study was designed to evaluate the effects of a diet rich in fish contaminated with MeHg, mi... more This study was designed to evaluate the effects of a diet rich in fish contaminated with MeHg, mimicking the typical diet of the Amazon riverside population, in rats. Animals were randomly assigned to one of three groups with eight rats in each group: Group I-control, received commercial ration; Group II-received a diet rich in uncontaminated fish; Group III-received a diet rich in fish contaminated with MeHg. Treatment time was 12 weeks. Oxidative stress markers were evaluated, as well as the effects of this diet on DNA stability, systolic blood pressure (SBP), nitric oxide (NO) levels and histological damage in different tissues. There was a significant increase in SBP values in rats fed with MeHg-contaminated fish diet after the 10th week of the treatment. As far as oxidative stress biomarkers are concerned, no differences were observed in reduced glutathione and protein carbonyl levels, glutathione peroxidase, catalase, superoxide dismutase or d-aminolevulinate dehydratase activities between the groups of animals receiving contaminated and uncontaminated fish diets. On the other hand, malondialdehyde levels increased significantly in rats fed with contaminated fish. NO levels were similar in all groups. DNA migration showed augmented in rats exposed to contaminated fish and histopathological analyses showed weak but significant leukocyte infiltration. Thus, we conclude that the MeHg-contaminated fish diet induced a slight lipid peroxidation and genotoxicity. However, these effects seem to be much less pronounced than when rats are exposed to aqueous solution containing CH 3 HgCl. Our findings support the contention that the chemical form of MeHg in fish or fish nutrients such as polyunsaturated fatty acids, Se or vitamin E could minimize the toxic effects of MeHg exposure in fisheating communities.
Environmental and Molecular Mutagenesis, 2012
Populations in the Amazon are exposed to organic mercury via consumption of contaminated foods. T... more Populations in the Amazon are exposed to organic mercury via consumption of contaminated foods. These ethnic groups consume a specific plant seed ''annatto'' which contains certain carotenoids. The aim of this study was to find out if these compounds (bixin, BIX and norbixin, NOR), protect against DNA-damage caused by the metal. Therefore, rats were treated orally with methylmercury (MeHg) and with the carotenoids under conditions that are relevant to humans. The animals were treated either with MeHg (30 lg/ kg/bw/day), BIX (0.1-10 mg/kg/bw/day), NOR (0.01-1.0 mg/kg/bw/day) or combinations of the metal compound and the carotenoids consecutively for 45 days. Subsequently, the glutathione levels (GSH) and the activity of catalase were determined, and DNA-damage was measured in hepatocytes and leukocytes using single cell gel electrophoresis assays. Treatment with the metal alone caused a decrease in the GSH levels (35%) and induced DNA damage, which resulted in increased DNA migration after electrophoresis in liver and blood cells, whereas no effects were seen with the carotenoids alone. When BIX or NOR were given in combination with organic mercury, the intermediate and the highest concentrations of the carotenoids (1.0 and 10.0 mg/kg/ bw/day BIX and 0.1 and 1.0 mg/kg/bw/day NOR) protected against DNA-damage. Furthermore, we found with both carotenoids, a moderate increase in the GSH levels in both metaltreated and untreated animals, while the activities of catalase remained unchanged. Our results indicate that consumption of BIX and NOR may protect humans against the adverse health effects caused by exposure to organic mercury. Environ.
Archives of Toxicology, 2011
Aim of the study was to find out whether consumption of quercetin (QC), an abundant flavonoid in ... more Aim of the study was to find out whether consumption of quercetin (QC), an abundant flavonoid in the human diet, protects against DNA damage caused by exposure to organic mercury. Therefore, rats were treated orally with methylmercury (MeHg) and the flavonoid with doses that reflect the human exposure. The animals received MeHg (30 μg/kg/bw/day), QC (0.5-50 mg/kg/bw/day), or combinations of both over 45 days. Subsequently, the glutathione levels (GSH) and the activities of glutathione peroxidase (GPx) and catalase (CAT) were determined, and DNA damage was measured in hepatocytes and peripheral leukocytes in single cell gel electrophoresis assays. MeHg decreased the concentration of GSH and the activity of GPx by 17 and 12%, respectively and caused DNA damage to liver and blood cells, while with QC no such effects were seen. When the flavonoid was given in combination with MeHg, the intermediate and the highest concentrations (5.0 and 50.0 mg/kg/bw/day) were found to cause DNA protection; DNA migration was reduced by 54 and 65% in the hepatocytes and by 27 and 36% in the leukocytes; furthermore, the reduction in GSH and GPx levels caused by MeHg treatment was restored. In summary, our results indicate that consumption of QC-rich foods may protect Hg-exposed humans against the adverse health effects of the metal.
Archives of Toxicology, 2010
Pharmaceutics
Metastatic prostate cancer (mPCa) is resistant to several chemotherapeutic agents. Brachydin A (B... more Metastatic prostate cancer (mPCa) is resistant to several chemotherapeutic agents. Brachydin A (BrA), a glycosylated flavonoid extracted from Fridericia platyphylla, displays a remarkable antitumoral effect against in vitro mPCa cells cultured as bidimensional (2D) monolayers. Considering that three-dimensional (3D) cell cultures provide a more accurate response to chemotherapeutic agents, this study investigated the antiproliferative/antimetastatic effects of BrA and the molecular mechanisms underlying its action in mPCa spheroids (DU145) in vitro. BrA at 60–100 μM was cytotoxic, altered spheroid morphology/volume, and suppressed cell migration and tumor invasiveness. High-content analysis revealed that BrA (60–100 µM) reduced mitochondrial membrane potential and increased apoptosis and necrosis markers, indicating that it triggered cell death mechanisms. Molecular analysis showed that (i) 24-h treatment with BrA (80–100 µM) increased the protein levels of DNA disruption markers (c...
Food and Chemical Toxicology, 2022
A diet deficient in donors of methyl group such as methionine affects DNA methylation and hepatic... more A diet deficient in donors of methyl group such as methionine affects DNA methylation and hepatic lipid metabolism. Methionine also affects other epigenetic mechanisms such as microRNAs. We investigated the effects of methionine-supplemented or methionine-deficient diets on the expression of chromatin-modifying genes, global DNA methylation, expression and methylation of genes related to lipid metabolism, and expression of microRNAs in mice liver. We fed female Swiss albino mice a control diet (0.3% methionine), a methionine-supplemented diet (2% methionine), and a methionine-deficient diet (0% methionine) for 10 weeks. The group of genes most affected by the supplemented diet was genes with histone and DNA methyltransferases activity, while the deficient diet most altered the expression histone methyltransferases genes. Both diets altered the global DNA methylation, expression, and gene-specific methylation of the lipid metabolism gene Apoa5. Finally, both diets altered the expression of several liver homeostasis-related microRNAs, such as miR-190b-5p, miR-130b-3p, miR-376c-3p, miR-411-5p, miR-29c-3p, miR-295-3p, and miR-467d-5p, with a more significant effect of the methionine-deficient diet. The effects of improper amount of methionine in the diet on liver pathologies might involve a cooperative action of chromatin-modifying genes, which results in an aberrant pattern of global and gene-specific methylation, and microRNAs responsible for liver homeostasis.
Journal of Medicinal Plants Research, Jul 18, 2011
Many tests have been done to ameliorate the side effects caused by doxorubicin (DXR) chemotherapy... more Many tests have been done to ameliorate the side effects caused by doxorubicin (DXR) chemotherapy. Croton cajucara is a plant that presents several biological beneficial properties. The aim of this study was to verify whether C. cajucara methanolic extract (EMeOH) prevents the DXR-induced testicular alterations and whether presents mutagenic or antimutagenic activities. Mice received DXR combined or not with EMeOH (312.5, 625 or 1250 mg/Kg) for 5 weeks. The fertility index and the micronucleous assay were realized in the male mice. The testes were removed and embedding in paraffin for the stereological and morphometric analyses. There were significant reductions in all parameters analyzed in the mice treated with DXR alone or with EMeOH. The plant extract doses evaluated presented no mutagenicity, antimutagenic properties and reduction of the DNA damage. Thus, EMeOH did not ameliorate the DXR-testicular damage, but the mutagenicity tests indicate a possible chemoprotective action of this plant extract.
Semina-ciencias Agrarias, 2017
Para combater efeitos genotoxicos de agentes quimicos, aditivos de alimentos e medicamentos que c... more Para combater efeitos genotoxicos de agentes quimicos, aditivos de alimentos e medicamentos que causam danos no DNA, estudos sobre quimioprevencao sao desenvolvidos com o proposito de reverter ou suprimir lesoes pre-malignas ou malignas por meio da utilizacao de compostos quimicos naturais ou sinteticos. Os fitoterapicos tem sido uma alternativa para quimioprevencao de doencas cronicas. Entre as plantas utilizadas na medicina popular brasileira destaca-se o genero Arrabidaea (familia Bignoniaceae). Diversas especies deste genero tem sido utilizadas na medicina tradicional com funcao antioxidante, antimicrobiana, antitumoral, anti-inflamatoria e adstringente. O presente estudo teve como objetivo avaliar os possiveis efeitos citotoxicos de quatro concentracoes (0,96; 1,50; 3,84 e 6,00 ?M) de brachydin A, um composto extraido das raizes de Arrabidaea brachypoda (DC) Bureau, em relacao ao processo de morte celular em linhagens celulares humanos de prostata normais (PNT2) e tumorais (PC-...
Immunobiology, 2021
In this review, we highlight the interaction of SARS-CoV-2 virus and host genomes, reporting the ... more In this review, we highlight the interaction of SARS-CoV-2 virus and host genomes, reporting the current studies on the sequence analysis of SARS-CoV-2 isolates and host genomes from diverse world populations. The main genetic variants that are present in both the virus and host genomes were particularly focused on the ACE2 and TMPRSS2 genes, and their impact on the patients' susceptibility to the virus infection and severity of the disease. Finally, the interaction of the virus and host non-coding RNAs is described in relation to their regulatory roles in target genes and/or signaling pathways critically associated with SARS-CoV-2 infection. Altogether, these studies provide a significant contribution to the knowledge of SARS-CoV-2 mechanisms of infection and COVID-19 pathogenesis. The described genetic variants and molecular factors involved in host/virus genome interactions have significantly contributed to defining patient risk groups, beyond those based on patients' age and comorbidities, and they are promising candidates to be potentially targeted in treatment strategies for COVID-19 and other viral infectious diseases.
Journal of Toxicology and Environmental Health, Part A, 2020
Brachydins (Br) A, B, and C are flavonoids extracted from Fridericia platyphylla (Cham.) L.G. Loh... more Brachydins (Br) A, B, and C are flavonoids extracted from Fridericia platyphylla (Cham.) L.G. Lohmann roots (synonym Arrabidaea brachypoda), whose extract previously exhibited cytotoxic and antitumor activity. In vitro cell culture of human prostate tumor cell line (PC-3) was used to determine cell viability as evidenced by MTT, neutral red, and LDH release using nine concentrations (0.24 to 30.72 µM) of each brachydin. A triple-fluorescent staining assay assessed the mechanism resulting in cell death. Genomic instability and protein expression were evaluated using comet assay and western blot analysis, respectively. The pro-oxidant status was analyzed using the5-(and-6)chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H 2 DCFDA) probe. The IC 50 values for brachydins BrA, BrB, and BrC were 23.41, 4.28, and 4.44 µM, respectively, and all compounds induced apoptosis and necrosis. BrB and BrC increased p21 levels indicating a possible G1 cell cycle arrest. BrA (6 µM) and BrB (3.84 µM) decreased phospho-AKT (AKT serine/threonine kinase) expression, which also influenced cell cycle and proliferation. BrA, BrB, and BrC elevated cleaved PARP (poly (ADP-ribose) polymerase), a protein related to DNA repair and induction of apoptotic processes. Therefore, this study determined the IC 50 values of brachydins in the PC-3 cell line as well as the influence on cell proliferation and cell death processes, such as apoptosis and necrosis, indicating the proteins involved in these processes.
Genetics and Molecular Biology, 2020
Polymorphic variants in the PTEN (rs2735343), PI3K (rs2699887), AKT1 (rs2494750), AR (rs17302090)... more Polymorphic variants in the PTEN (rs2735343), PI3K (rs2699887), AKT1 (rs2494750), AR (rs17302090), and AMACR (rs3195676) genes were evaluated as possible molecular markers of susceptibility, prognosis, and progression of prostate cancer (PCa), in a case-control study. Samples consisted of 277 patients with PCa and 277 controls from Londrina, PR, Brazil. SNPs were analyzed by real-time PCR. A family history of cancer, including PCa, as well as level of schooling were risk factors for PCa. The data were obtained via logistic regression, using odds ratios with a CI 95%. The genotypes of AKT1 and AKT1+AR demonstrated an association with protection for the disease. The combination of SNPs with the histopathological tumor data between allele variants of AMACR, AKT1+AR, and AKT1+AMACR indicated an association with protection against seminal vesicle invasion. The polymorphisms AKT1+AR and PI3K+AR were associated with protection against tumor bilaterality. The genotype combinations PTEN+AMACR and PTEN+AR were associated with the risk of extracapsular extension. Of the five genes studied, two were associated with protection for PCa, four were associated with protection for some prognostic variables, and only one was associated with risk. Thus, these SNPs are candidates for markers to discriminate men with better or worse prognosis for PCa.
Cytotechnology, 2016
Brazilian flora biodiversity has been widely investigated to identify effective and safe phytothe... more Brazilian flora biodiversity has been widely investigated to identify effective and safe phytotherapeutic compounds. Among the investigated plant species, the Byrsonima genus exhibits promising biological activities. This study aimed at evaluating the cytotoxicity of B. correifolia, B. verbascifolia, B. fagifolia and B. intermedia extracts using different assays in two cell lines (primary gastric and HepG2 cells). The different extract concentrations effects on cell viability were assayed using the MTT, aquabluer, neutral red and LDH assays. Non-cytotoxic concentrations were selected to generate cell proliferation curves and to assess cell cycle kinetics by flow cytometry. Byrsonima extracts differentially affected cell viability depending on the metabolic cellular state and the biological parameter evaluated. B. fagifolia and B. intermedia extracts exhibited lower cytotoxic effects than B. correifolia and B. verbascifolia in all assays. The results obtained with LDH and flow cytometry assays were more reliable, suggesting that they can be useful in the screening for herbal medicine and to further characterize these extracts as phytotherapeutic compounds.
Journal of Ethnopharmacology, 2015
Ethnopharmacological relevance: The Brazilian "Cerrado" is an important source of natural product... more Ethnopharmacological relevance: The Brazilian "Cerrado" is an important source of natural products, such as Myrcia bella Cambess (MB, also known as "mercurinho"). MB leaves are popularly used for the treatment of diabetes and gastrointestinal disorders; however, only its hypoglycemic activity has been experimentally described. Aim of the study: Because MB is used to treat gastrointestinal disorders, the present study characterized biological activities of hydroalcoholic MB extract in human normal and tumor gastric cells. Materials and methods: Cytotoxic, antiproliferative, genotoxic and protective effects were evaluated, as well as the effects of the MB extract on gene expression. Results: The MB extract induced cytotoxicity in tumor cells at lower concentrations compared with normal cells as assessed by the MTT assay. Moreover, the MB extract induced necrosis based on acridine orange/ethidium bromide staining. An antiproliferative effect was evidenced through an arrest in the G2/ M phase detected by flow cytometry and a decrease in the nuclear division index using the cytokinesisblock micronucleus cytome assay. Cells treated with MB extract combined with doxorubicin (DXR) showed increased NUBDs, which may be related to the gene amplification of CCND1. Antimutagenic effects were also observed and may be associated with the antioxidant activities detected using the CM-H 2 DCFDA probe. Conclusions: Our findings showed the following: (a) high concentrations of MB induced cytotoxicity and cell death by necrosis; (b) its antiproliferative effect was associated with G2/M arrest; and (c) its antioxidant activity could be responsible for the observed antimutagenic effects and for protective effects against gastrointestinal disorders previously described to MB. Although these effects are not specific to normal or tumor cells, they provide a panel of biological activities for further exploration.
Mutagenesis, 2015
Machaerium hirtum (Vell.) Stellfeld (M.hirtum) is a plant known as 'jacarandá-bico-de-pato' whose... more Machaerium hirtum (Vell.) Stellfeld (M.hirtum) is a plant known as 'jacarandá-bico-de-pato' whose bark is commonly used against diarrhea, cough and cancer. The aim of this study was to phytochemically characterise the hydroethanolic extract of this plant, investigate its antimutagenic activities using the Ames test and evaluate its effects on cell viability, genomic instability, gene expression and cell protection in human hepatocellular carcinoma cells (HepG2). Antimutagenic activity was assessed by simultaneous pre-and post-treatment with direct and indirect mutagens, such as 4-nitro-o-phenylenediamine (NPD), mitomycin C (MMC), benzo[a]pyrene (B[a]P) and aflatoxin B 1 (AFB 1), using the Ames test, cytokinesis blocking micronucleus and apoptosis assays. Only 3 of the 10 concentrations evaluated in the MTT assay were cytotoxic in HepG2 cells. Micronucleated or apoptotic cells were not observed with any of the tested concentrations, and there were no mutagenic effects in the bacterial system. However, the Nuclear Division Index and flow cytometry data showed a decrease in cell proliferation. The extract showed an inhibitory effect against direct (NPD) and indirect mutagens (B[a]P and AFB 1). Furthermore, pre-and post-treated cells showed significant reduction in the number of apoptotic and micronucleated cells. This effect is not likely to be associated with the modulation of antioxidant genes, as shown by the RT-qPCR results. Six known flavonoids were identified in the hydroethanolic extract of Machaerium hirtum leaves, and their structures were elucidated by spectroscopic and spectrophotometric methods. The presence of the antioxidants apigenin and luteolin may explain these protective effects, because these components can inhibit the formation of reactive species and prevent apoptosis
Many tests have been done to ameliorate the side effects caused by doxorubicin (DXR) chemotherapy... more Many tests have been done to ameliorate the side effects caused by doxorubicin (DXR) chemotherapy. Croton cajucara is a plant that presents several biological beneficial properties. The aim of this study was to verify whether C. cajucara methanolic extract (EMeOH) prevents the DXR-induced testicular alterations and whether presents mutagenic or antimutagenic activities. Mice received DXR combined or not with EMeOH (312.5, 625 or 1250 mg/Kg) for 5 weeks. The fertility index and the micronucleous assay were realized in the male mice. The testes were removed and embedding in paraffin for the stereological and morphometric analyses. There were significant reductions in all parameters analyzed in the mice treated with DXR alone or with EMeOH. The plant extract doses evaluated presented no mutagenicity, antimutagenic properties and reduction of the DNA damage. Thus, EMeOH did not ameliorate the DXR-testicular damage, but the mutagenicity tests indicate a possible chemoprotective action of this plant extract.
Uploads
Papers by Juliana Mara Serpeloni