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Braz. J. Pharm. Sci. (Online) ; 59: e23037, 2023. tab, graf
Article in English | LILACS | ID: biblio-1520322


Abstract Resolution 658/2022 of the Brazilian Regulatory Agency requires the determination of the permitted daily exposure (PDE) of pharmaceutical agents. Ginkgo biloba L. is used therapeutically to treat memory deficits and other brain diseases. However, published results indicate that more studies are needed to confirm the safety of Ginkgo biloba. This study aimed to evaluate the dry extract of Ginkgo biloba L. leaves PDE as an ingredient in an oral pharmaceutical product in preclinical studies using mice. Acute oral toxicity and repeated dose experiments were performed based on OECD guidelines, as well as genotoxicity tests. The results indicate that Ginkgo biloba L. has low acute toxicity, no liver toxicity, and does not alter blood glucose levels. No changes in weight gain were observed, but food intake decreased in males during the first week of treatment at the highest dose. Hematological parameters were not altered in males, whereas females presented lower leukocyte and lymphocyte counts and higher neutrophil counts at the highest dose. The lipid profile was not altered in males, whereas total cholesterol was increased in females. The estimated PDE was 0.1 mg/day and, when related to the maximum residual concentration, indicates that the cleaning process used is safe and does not require reassessment.

Animals , Male , Female , Mice , Plant Extracts/agonists , Genotoxicity , Ginkgo Extract/analysis , Brain Diseases/pathology , Pharmaceutical Preparations , Lymphocyte Count/classification , Toxicity
Arch. latinoam. nutr ; 72(3): 205-217, sept. 2022. ilus, tab, graf
Article in Spanish | LILACS, LIVECS | ID: biblio-1399287


Las catequinas del té verde (Camellia sinensis) (CTV) presentan efectos benéficos para la salud asociados a su potencial antioxidante. Por otra parte, el estrés oxidante es una de las vías de inducción de daño genotóxico. De ahí que, en la presente revisión se realizó un análisis de los efectos antigenotóxicos y genotóxicos de las CTV, haciendo énfasis en las vías implicadas en estos procesos y sus efectos en la salud. Se realizó una revisión de artículos indexados en las bases de datos de PubMed® y Science Direct® (2021) con las palabras clave "green tea" y "green tea catechins". Se delimitaron los estudios utilizando los operadores booleanos "AND", "OR" y "NOT" ("antigenotoxic", "genotoxic", "antioxidant" y "prooxidant"). En su mayoría se consideraron las publicaciones del 2016 al 2021. Se observó que los efectos benéficos en la salud de las CTV están relacionados con: a) su actividad antioxidante mediante la captura, inhibición y prevención de la formación de las especies reactivas de oxígeno; b) la regulación del sistema antioxidante endógeno; c) la activación de los mecanismos de reparación al contribuir en la eliminación del aducto 8-hidroxi-2'-desoxiguanosina; d) la inducción de apoptosis en células con daño al ADN; y e) la inhibición de la inflamación relacionada con su actividad antiapoptótica. Si bien, en algunos de los estudios se reportaron efectos genotóxicos, estos a su vez contribuyeron en la eliminación de células con daño genético, por lo que, no se puede considerar del todo a la actividad genotóxica de las CTV como perjudiciales para la salud(AU)

The green tea catechins (Camellia sinensis) (CTV) have beneficial effects for health associated with their antioxidant potential. Moreover, oxidative stress is one of the pathways for inducing genotoxic damage. Hence, in this review, an analysis of the antigenotoxic and genotoxic effects of CTV was carried out, emphasizing the pathways involved in these processes and their effects on health. A review of articles indexed in the PubMed® and ScienceDirect® (2021) databases with the keywords "green tea" and "green tea catechins" was carried out. Studies were delimited using the Boolean operators "AND", "OR" and "NOT" ("antigenotoxic", "genotoxic", "antioxidant" and "prooxidant"). For the most part, publications from 2016 to 2021 were considered. It was observed that the beneficial health effects of CTVs are related to: a) their antioxidant activity through the capture, inhibition and prevention of the formation of reactive oxygen species; b) the regulation of the endogenous antioxidant system; c) the activation of the repair mechanisms by contributing to the elimination of the 8-hydroxy-2'-deoxyguanosine adduct; d) the induction of apoptosis in cells with DNA damage; and e) the inhibition of inflammation related to its antiapoptotic activity. Although some of the studies reported genotoxic effects, these in turn contributed to the elimination of cells with genetic damage. Therefore, the genotoxic activity of CTV cannot be considered as harmful to health

Humans , Animals , Tea/chemistry , Catechin/toxicity , Oxidative Stress/drug effects , Genotoxicity , Antioxidants/toxicity , DNA Damage/drug effects , Reactive Oxygen Species , Apoptosis/drug effects
Rev. Ciênc. Méd. Biol. (Impr.) ; 21(1): 53-59, maio 05,2022. fig, tab
Article in Portuguese | LILACS | ID: biblio-1370669


Introdução: as terapias alternativas que utilizam plantas medicinais e fitoterápicos são bastante comuns no Brasil. Dentre várias espécies vegetais brasileiras utilizadas em terapias destacam-se as espécies da família Malvaceae. Objetivos: o presente estudo teve como objetivo avaliar a citotoxicidade in vitro e a genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke espécie brasileira pertencente à família Malvaceae. Metodologia: métodos in vitro foram utilizados para verificar o potencial citotóxico por meio de ensaios hemolíticos e anti-hemolíticos e da análise genotóxica ex-vivo. O Extrato Etanólico Bruto (EEB) e Fração Clorofórmico (FC) foram obtidos na amostra vegetal utilizada neste estudo. Resultados: os produtos EEB-Pg e FC-Pg apresentaram baixo efeito citotóxico apenas nas concentrações de 50 e 100 µg / mL. As amostras expostas às concentrações de 500 e 1000 µg / mL apresentaram índice hemolítico alto a moderado com lise superior a 60%. Foi descrito efeito anti-hemolítico moderado em todas as amostras tratadas com 500 e 1000 µg / mL, com hemólise < 60%. Além disso, os compostos mostraram baixo efeito genotóxico ex-vivo, com um índice geral de células normais superior a 84% em todas as concentrações. Conclusões: os resultados sugerem um baixo perfil tóxico dos compostos obtidos da espécie Pavonia glazioviana, indicando limites seguros para o uso desses produtos naturais.

Introduction: alternative therapies using medicinal plants and herbal medicines are quite common in Brazil. Among several Brazilian plant species used in therapies, the species of the Malvaceae family stand out. Objetctives: the present study aimed to evaluate the in vitro cytotoxicity and ex-vivo genotoxicity in compounds of the Brazilian Pavonia glazioviana Gürke belonging to the Malvaceae family. Methodology: in vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study. Results: the CEE-Pg and CF-Pg products only showed a low cytotoxic effect at the concentrations of 50 and 100 µg/mL. The exposure to the concentrations of 500 and 1000 µg/mL showed a high to moderate hemolytic index with lysis higher than 60%. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60%. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84% at all concentrations. Conclusion: the results suggest a low toxic profile of the compounds obtained from the Pavonia glazioviana Gürke species belonging to the Malvaceae family, indicating safe limits for the use of these natural products.

Humans , Plant Extracts/pharmacology , Malvaceae/chemistry , Genotoxicity , Hemolytic Agents/pharmacology , Plants, Medicinal/chemistry , Dose-Response Relationship, Drug
Braz. J. Pharm. Sci. (Online) ; 58: e20096, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403677


Abstract Dexchlorpheniramine is a first-generation classical antihistamine, clinically used to treat allergies. The main objective of our study was to evaluate the effects of the dexchlorpheniramine reference standard (DCPA Ref. St) and a pharmaceutical formula on DNA in human peripheral blood mononuclear cells (PBMCs). We exposed PBMCs to five different concentrations (0.5, 2.5, 5, 10, and 50 ng/mL) of DCPA Ref. St DCPA Ref. St and pharmaceutical formula in order to evaluate their cytotoxic, genotoxic, and mutagenic potential. The results showed that both dexchlorpheniramine formulations did not affect PBMC viability and CD3+, CD4+, or CD8+ lymphocyte subpopulations. The DCPA Ref. St and pharmaceutical formula neither induced genotoxic or mutagenic effects nor numerical or structural chromosomal alterations in PBMCs after 24 hours of exposure.

Humans , Leukocytes, Mononuclear/metabolism , Cytotoxicity, Immunologic , Drug Compounding , Genotoxicity , Mutagenicity Tests , DNA/analysis , Histamine Antagonists/adverse effects , Hypersensitivity/complications
Braz. J. Pharm. Sci. (Online) ; 58: e19221, 2022. tab, graf
Article in English | LILACS | ID: biblio-1374557


Abstract The purpose of the current work was to assess a possible role of cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 2 (NAT2) in the metabolic activation of 2,6-dimethylaniline (2,6-DMA) and also clarify the function of DNA repair in affecting the ultimate mutagenic potency. Two cell lines, nucleotide excision repair (NER)-deficient 5P3NAT2 and proficient 5P3NAT2R9 both expressing CYP1A2 and NAT2, were treated with 2,6-DMA for 48 h or its metabolites for 1 h. Cell survival determined by trypan blue exclusion and MTT assays, and 8-azaadenine-resistant mutants at the adenine phosphoribosyltransferase (aprt) gene locus were evaluated. 5P3NAT2 and 5P3NAT2R9 cells treated with 2,6-DMA and its metabolites showed a dose-dependent increase in cytotoxicity and mutant fraction; N-OH-2,6-DMA and 2,6-DMAP in serum-free α-minimal essential medium (MEM) are more potent than 2,6-DMA in complete MEM. 5P3NAT2 cells was more sensitive to the cytotoxic and mutagenic action than 5P3NAT2R9 cells. H2DCFH-DA assay showed dose-dependent ROS production under 2,6- DMAP treatment. These findings indicate that the genotoxic effects of 2,6-DMA are mediated by CYP1A2 activation via N-hydroxylation and the subsequent esterification by the phase II conjugation enzyme NAT2, and through the generation of ROS by hydroxylamine and/or aminophenol metabolites. NER status is also an important contributor

Cells/classification , Cytochrome P-450 CYP1A2/analysis , Genotoxicity , Cell Line/classification , Hydroxylamine/agonists , DNA Repair
São Paulo; s.n; s.n; 2022. 172 p. tab, graf.
Thesis in English | LILACS | ID: biblio-1378625


The solar ultraviolet (UV) radiation that reaches the Earth is composed of 95% of UVA (320 to 400 nm) and 5% of UVB (280 to 320 nm) radiation. UVB is carcinogenic, generating potentially mutagenic DNA lesions. The solar UVA radiation also causes DNA damage, but this fact does not fully account for its biological impact. UVA is absorbed by non-DNA cellular chromophores, generating reactive oxygen species such as singlet oxygen. Knowing the proteome mediates stress responses in cells, here we investigated the cellular effects of a non-cytotoxic dose of UVA radiation, equivalent to about 20 minutes of midday sun exposure, on the proteome of human keratinocytes. Using a combination of mass spectrometry-based proteomics, bioinformatics, and conventional biochemical assays, we analyzed two aspects of UVA-induced stress: spatial remodeling of the proteome in subcellular compartments 30 minutes after stress and long-term changes in protein levels and secretion (24 hours and 7 days postirradiation). In the first part of this thesis, we quantified and assigned subcellular localization for over 3000 proteins, of which about 600 potentially redistribute upon UVA exposure. Protein redistributions were accompanied by redox modulations, mitochondrial fragmentation and DNA damage. In the second part of the work, our results showed that primary human keratinocytes enter senescence upon exposure to a single dose of UVA, mounting antioxidant and inflammatory responses. Cells under UVA-induced senescence further elicit paracrine responses in neighboring premalignant HaCaT epithelial cells via inflammatory mediators. Altogether, these results reiterate the role of UVA radiation as a potent metabolic stressor in the skin

A radiação ultravioleta (UV) solar que atinge a superfície terrestre é composta por 95% de radiação UVA (320 a 400 nm) e 5% de radiação UVB (280 a 320 nm). A radiação UVB é carcinogênica e gera lesões potencialmente mutagênicas no DNA. A radiação UVA solar também gera danos no DNA, mas a genotoxicidade dessa radiação não explica inteiramente o seu impacto biológico. Atualmente, sabe-se que a radiação UVA é absorvida por cromóforos celulares, gerando espécies reativas de oxigênio, como o oxigênio singlete. Sabendo que o proteoma é um mediador de respostas ao estresse celular, nós investigamos os efeitos celulares de uma dose não-citotóxica de radiação UVA, equivalente a cerca de 20 minutos de exposição ao sol, no proteoma de queratinócitos humanos. Utilizando espectrometria de massas, bioinformática e ensaios bioquímicos convencionais, nós analisamos dois aspectos do estresse induzido por radiação UVA: o remodelamento espacial do proteoma 30 minutos depois do estresse e alterações nos níveis e na secreção de proteínas no longo prazo (24 horas e 7 dias depois da irradiação). Na primeira parte desta tese, nós quantificamos e atribuímos classificações de localização subcelular a mais de 3000 proteínas. Dentre essas proteínas, 600 tem potencialmente a sua distribuição subcelular alterada em resposta à radiação. As redistribuições subcelulares são acompanhadas de modulações redox, fragmentação mitocondrial e danos no DNA. Na segunda parte da tese, os nossos resultados mostraram que queratinócitos humanos primários entram em senescência sob exposição a uma única dose de radiação UVA, montando respostas antioxidantes e pró-inflamatórias. Células sob senescência induzida por UVA, por sua vez, desencadeiam respostas parácrinas em queratinócitos pré-tumorais (células HaCaT) por meio de mediadores inflamatórios. Em conjunto, esses resultados reiteram o papel da radiação UVA como um potente estressor metabólico em células da pele

Skin , Ultraviolet Rays/adverse effects , Keratinocytes/chemistry , Proteomics/classification , Radiation Dosage , Mass Spectrometry/methods , DNA , Epithelial Cells/classification , Genotoxicity/adverse effects , HaCaT Cells/classification , Antioxidants/adverse effects
Rev. peru. med. exp. salud publica ; 38(4): 587-594, oct.-dic. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1365918


RESUMEN Objetivos. Determinar el efecto genotóxico de la tartrazina en linfocitos de sangre periférica de Mus musculus BALB/c. Materiales y métodos. Se realizó un estudio experimental, a través de cinco grupos, con cinco ratones en cada uno. Se les registró el peso durante 17 semanas y, en la semana 15 se les administró suero fisiológico (control negativo), dicromato de potasio 25 mg/kg de peso corporal (pc) (control positivo) y tartrazina a dosis de 0,75 mg/kg pc, 7,5 mg/kg pc y 75 mg/kg pc, durante siete días, a excepción del control positivo que fue en dosis única. Luego, cada 24 h se obtuvo una muestra de sangre periférica de la cola y se realizó el frotis, secado y coloración. Posteriormente, se realizó el conteo de 1000 linfocitos por muestra de cada ratón, en todos los tratamientos. Resultados. Los tres tratamientos con tartrazina no causaron diferencias significativas en el peso de ratones a la semana 15, pero sí produjeron diferencias significativas en la frecuencia de linfocitos micronucleados, siendo el tratamiento con tartrazina de 75 mg/kg pc el de mayor efecto genotóxico, induciendo un promedio de 1,63 ± 0,08 linfocitos micronucleados, comparado con el control positivo que generó un promedio de 1,42 ± 0,08 linfocitos micronucleados. Conclusiones. La tartrazina produjo un efecto genotóxico, incrementando el número de linfocitos micronucleados, a dosis de 0,75; 7,5 y 75 mg/kg pc y no afecta el peso corporal durante siete días de administración en M. musculus BALB/c.

ABSTRACT Objectives. To determine the genotoxic effect of tartrazine on peripheral blood lymphocytes of BALB/c Mus musculus. Materials and methods. An experimental study was carried out using five groups, with five mice in each group. Their weight was registered for 17 weeks, and at week 15 they were administered physiological saline solution (negative control), potassium dichromate at 25 mg/kg body weight (bw) (positive control) and tartrazine at doses of 0.75 mg/kg bw, 7.5 mg/kg bw and 75 mg/kg bw, for seven days, with the exception of the positive control which was a single dose. Then, every 24 hours, a peripheral blood sample was obtained from the tail, which was then smeared, dried and stained. Subsequently, 1000 lymphocytes were counted for each sample from each mouse, for all treatment groups. Results. The three tartrazine treatments did not cause significant differences in the weight of mice at week 15, but did produce significant differences in the frequency of micronucleated lymphocytes, with the 75 mg/kg bw tartrazine treatment having the greatest genotoxic effect, inducing an average of 1.63 ± 0.08 micronucleated lymphocytes, compared to the positive control which obtained an average of 1.42 ± 0.08 micronucleated lymphocytes. Conclusions. Tartrazine produced a genotoxic effect, increasing the number of micronucleated lymphocytes, at doses of 0.75; 7.5 and 75 mg/kg bw and did not affect body weight during seven days of administration to BALB/c M. musculus.

Animals , Mice , Tartrazine , Lymphocytes , Genotoxicity , Mice , Micronucleus Tests , Toxicity Tests , Micronuclei, Chromosome-Defective , Recommended Dietary Allowances , Food Additives , Mice, Inbred Strains
Araçatuba; s.n; 2021. 66 p. graf, ilus.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1434346


O objetivo deste estudo foi investigar a ação sinérgica do risedronato de sódio sistêmico e da genisteína administrada localmente, através da funcionalização de implantes, de ratas submetidas a ovariectomia e com hábitos de mimetizam a síndrome metabólica. A parte in vitro deste estudo foi executado em 2 etapas. Na primeira etapa, foi realizada a funcionalização da superfície de discos/implantes com genistína na concentração de 100 µM pela técnica layer by layer (lbl). Na segunda etapa foram feitos testes biológicos em culturas de células, para avaliar as propriedades da superfície funcionalizada, quanto às respostas osteogênicas. Para a cultura de células foram utilizadas células mesenquimais diferenciadas em osteoblastos, isoladas de fêmures de ratos. Após a validação pelos testes executados nas superfícies funcionalizadas, foi realizado estudo in vivo (3ª etapa). Para tanto, no dia 0, as ratas Wistar adultas jovens, fêmeas (n=64) foram divididas em 4 grupos: 1- SHAM (n= 16), animais foram submetidos à ovariectomia (OVX) fictícia e dieta balanceada. 2- SHAM Síndrome Metabólica (SM) (n=16), animais foram submetidos à ovariectomia fictícia e dieta de cafeteria. 3- OVX SM (n=16), animais foram submetidos à ovariectomia bilateral e dieta de cafeteria. 4- OVX SM Risedronato (RIS) (n=16), animais foram submetidos à ovariectomia bilateral, dieta de cafeteria e tratadas com risedronato de sódio. Em cada grupo há 2 subgrupos: A- implantes convencionais e B- implantes funcionalizados com genisteína. No dia 30, foi iniciado o tratamento medicamentoso com risedronato de sódio, na concentração de 0,35mg/kg, ou apenas solução salina, via gavagem, 1 vez por semana. Passados 60 dias da medicação (dia 90), todos os animais foram submetidos à cirurgia para exodontia dos 1os molares superiores bilateralmente e, imediatamente, no alvéolo da raiz mesial, foi instalado os implantes com superfície convencional ou funcionalizada. Os animais foram eutanasiados aos 28 dias (dia 118) após a instalação dos implantes para mensuração do torque de falha na interface osso implante em N/cm. Os dados foram submetidos ao teste de homocedasticidade (Shapiro Wilk). Houve a confirmação de distribuição normal dos dados amostrais e na sequência, foi realizado o teste paramétrico ANOVA One Way or Two Way, seguido do pós teste de Tukey, com o nível de significância de 5% (p< 0,05). Concluiu-se que, a concentração de 100 µM da genisteína manteve a viabilidade celular e resultados favoráveis quanto a genotoxicidade. A dieta de cafeteria e a ovariectomia bilateral mimetizam a síndrome metabólica e a predisposição para osteoporose por deficiência de esteroides gonadais. E, a ação sinérgica entre fármaco sistêmico (risedronato de sódio) e genisteína local foi promissora para a melhora no processo de reparo periimplantar, principalmente no grupo SHAM e OVX SM RIS(AU)

The aim of this study was to investigate the synergistic action of systemic risedronate sodium and locally administered genistein, through implant functionalization, of rats submitted to ovariectomy and with habits mimicking the metabolic syndrome. The in vitro part of this study was performed in 2 steps. In the first step, the surface functionalization of discs/implants was performed with genistein at a concentration of 100 µM by the layer by layer (lbl) technique. In the second step biological tests were performed in cell cultures to evaluate the properties of the functionalized surface for osteogenic responses. For the cell culture, mesenchymal cells differentiated into osteoblasts, isolated from rat femurs, were used. After validation by tests performed on the functionalized surfaces, the in vivo study (third test) was performed. For this purpose, on day 0, young adult female Wistar rats (n=64) were divided into 4 groups: 1- SHAM (n=16), animals were submitted to sham ovariectomy (OVX) and balanced diet. 2- SHAM Metabolic Syndrome (MS) (n=16), animals were submitted to sham ovariectomy and cafeteria diet. 3- OVX SM (n=16), animals underwent bilateral ovariectomy and cafeteria diet. 4- OVX SM Risedronate (RIS) (n=16), animals underwent bilateral ovariectomy, cafeteria diet and treated with risedronate sodium. In each group there are 2 subgroups: A- conventional implants and B- implants functionalized with genistein. On day 30, drug treatment was started with risedronate sodium, at a concentration of 0.35 mg/kg, or just saline solution, via gavage, once a week. After 60 days of medication (day 90), all animals underwent surgery to extract the 1st upper molars bilaterally, and implants with conventional or functionalized surfaces were immediately installed in the mesial root alveolus. The animals were euthanized at 28 days (day 118) after implant installation to measure the failure torque at the implant-bone interface in N/cm. The data were submitted to the homoscedasticity test (Shapiro Wilk). The normal distribution of the sample data was confirmed and then the parametric One Way or Two Way ANOVA test was performed, followed by Tukey's post-test, with a significance level of 5% (p< 0.05). It was concluded that, the concentration of 100 µM of genistein maintained cell viability and favorable results regarding genotoxicity. The cafeteria diet and bilateral ovariectomy mimic the metabolic syndrome and predisposition to osteoporosis by gonadal steroid deficiency. And, the synergistic action between systemic drug (risedronate sodium) and local genistein was promising for the improvement in the periimplant repair process, especially in the SHAM and OVX SM RIS groups(AU)

Rats , Gonadal Steroid Hormones , Dental Implants , Osseointegration , Genistein , Metabolic Syndrome , Risedronic Acid , Osteoporosis , Surgery, Oral , Bone and Bones , Ovariectomy , Cell Survival , Rats, Wistar , Genotoxicity
Belo Horizonte; s.n; 2021. 115 p. ilus.
Thesis in Portuguese | LILACS, BBO | ID: biblio-1344175


No mercado encontramos uma grande variedade de materiais endodônticos disponibilizados para uso clínico, mas diversos estudos mostram divergências de opiniões com relação ao comportamento biológico dos diferentes materiais. Este trabalho teve como objetivos investigar a viabilidade celular, a expressão de genes envolvidos na plasticidade celular e a diferenciação celular em culturas de células- tronco recuperadas de polpa dentária humana (hDPSCs) quando em contato com quatro materiais endodônticos (Endofill, Pulp Canal Sealer, Sealer 26, MTA) rotineiramente utilizados na clínica odontológica. Objetivou também, por meio de uma revisão sistemática, analisar a biocompatibilidade de cimentos de uso endodôntico sobre células tronco de origem dental. Para isto, o metabolismo celular das hDPSCs, quando em contato com os capilares contendo ou não os cimentos, foi avaliado pelo ensaio de MTT (24 e 48 horas) e a viabilidade celular foi analisada pelo ensaio de exclusão do azul de tripan (48 horas). A plasticidade celular, na presença dos capilares contendo ou não os cimentos, foi avaliada pela expressão gênica dos marcadores CD34, CD45, Nestin, CD105, Nanog e OCT-4 por PCR. Finalmente, a diferenciação celular frente aos cimentos endodônticos foi verificada pela expressão dos genes RUNX2, ALP, OC/BGLAP e DMP1 por RT-PCR. Os dados foram analisados pelo teste ANOVA com correção de Bonferroni (p<0.05). Observou-se que os cimentos Pulp Canal Sealer e o Endofill reduziram significativamente a viabilidade e o metabolismo celular quando comparados ao controle após 48 horas (p<0.001). O MTA e o Sealer 26 não interferiram na viabilidade celular em ambos os períodos de avaliação (p>0.05). As hDPSCs, quando cultivadas na presença do MTA e Sealer 26, expressaram os marcadores Nestin, CD105, NANOG e OCT-4, e não expressaram CD34 e CD45. Por sua vez, o MTA e o Sealer 26 interferiram positivamente ou negativamente na expressão gênica de DMP1, OC/BGLAP e RUNX2 em relação ao grupo controle (p<0.05), mas não houve diferença significativa em relação à expressão gênica de ALP (p>0.05). Portanto, MTA e Sealer 26 demonstram boa compatibilidade biológica quando na presença das hDPSCs. A revisão sistemática demonstrou que a maioria dos materiais, apresentam boa compatibilidade quando em contato com as células tronco, estando aptos a serem utilizados na prática clínica.

On the market, we found a wide variety of endodontics cements available for clinical use, but several studies show divergences of opinion regarding the biological behavior of these different materials. This work aimed to investigate cell viability and metabolism, an expression of genes involved in cell plasticity and cell differentiation in stem cell cultures recovered from human dental pulp (hDPSCs) when in contact with four endodontic cements (Endofill, MTA, Pulp Canal Sealer, Sealer 26) routinely used in endodontic clinic. It also aimed, through a systematic review, to analyze the biocompatibility of endodontic materials on dental stem cells. For this, the viability and metabolism of hDPSCs, when it comes into contact with capillaries that included or not cements, was assessed by MTT assay (24 and 48 hours) and exclusion of trypan blue assay (48 hours). Cellular plasticity, with the presence of capillaries containing or not sealers, was evaluated by the genetic expression of the markers CD34, CD45, Nestin, CD105, Nanog and OCT-4 by PCR. Finally, cell differentiation from endodontics sealers was verified by the expression of the RUNX2, ALP, OC/BGLAP and DMP1 genes by RT-PCR. The data were analyzed using the ANOVA test with Bonferroni correction (p<0.05). We note that Pulp Canal Sealer and Endofill sealers decrease cell viability and cellular metabolism when compared to control after 48 hours (p<0.001). MTA and Sealer 26 did not interfere with cell viability in the two evaluation periods (p>0.05). hDPSCs, when grown in the presence of MTA and Sealer 26, express the Nestin, CD105, NANOG and OCT-4 markers, and do not express CD34 and CD45. In turn, MTA and Sealer 26 interfered in the gene expression of DMP1, OC/BGLAP and RUNX2 in relation to the control group (p<0.05), but did not find a significant difference in relation to the ALP gene expression (p>0.05). Therefore, MTA and Sealer 26 demonstrate good biological compatibility when in the presence of hDPSCs. The systematic review showed that almost all materials have good compatibility when in contact with stem cells, being able to be used in clinical practice.

Cytotoxicity, Immunologic , Dental Cements , Dental Pulp , Endodontics , Genotoxicity , Mesenchymal Stem Cells
São Paulo; s.n; s.n; 2021. 127 p. tab, graf.
Thesis in Portuguese | LILACS | ID: biblio-1396077


A inibição de alvos específicos como metaloproteinase de matriz (MMP) e histona desacetilase (HDAC) é amplamente estudada para impedir o progresso do câncer. Foi estabelecido que a inibição concomitante de MMP e HDAC é eficaz no combate de tumores sólidos e hematológicos. Ambos os alvos possuem um íon Zn2+ em seu sítio ativo, fundamental para a atividade destas enzimas. A alta afinidade dos inibidores conhecidos de MMP e de HDAC é conferida, principalmente, por um potente grupo ligante de zinco (ZBG). O ácido hidroxâmico é o ZBG mais potente conhecido atualmente, entretanto, este apresenta instabilidade farmacocinética, levando a ineficácia e genotoxicidade em testes clínicos. Frente a este contexto, o presente trabalho teve como objetivo o planejamento, síntese, modelagem molecular e avaliação biológica de novos inibidores duais MMP/HDAC não-hidroxamatos. Os compostos foram planejados utilizando estratégias de hibridação molecular, a partir de arcabouços provenientes inibidores de HDAC e MMP, gerando compostos arilsulfonamídicos com variações no tipo de ZBG inserido e na sua respectiva posição relativa na estrutura geral. Foram sintetizados sete análogos, em duas a três etapas reacionais, utilizando métodos de sulfonilação e acoplamento com agentes condensantes, partindo dos ésteres para e meta aminobenzoicos. Os rendimentos globais variaram de 25% a 55% e os produtos obtidos foram caracterizados por RMN 1H e 13C, LC/MS, CLAE e ponto de fusão. Os compostos tiveram sua atividade citotóxica avaliada em células HOG (oligodendroma) e T98G (glioblastoma), dentre os quais o 6a, que possui o ZBG 2-amino anilida, foi o mais promissor, apresentando atividade nas duas linhagens na casa de nM. Ensaios de coordenação com Fe2+ comprovaram a capacidade quelante dos análogos contendo ácido hidroxâmico e dos demais compostos citotóxicos, 4a e 4b (ZBG-2, salicilal-hidrazona), o que não foi observado para o composto 6a. Os estudos de ancoramento molecular permitiram sugerir um modo de interação para todos os ZBG propostos frente aos respectivos alvos (HDAC e MMP), sendo observado que o ZBG 4 (2-amino anilida) faria a interação de modo monodentado com a HDAC, enquanto não seria possível o encaixe no sítio catalítico da MMP. Conclui-se, portanto, que o planejamento proposto permitiu a obtenção de compostos promissores como antitumorais, e que a substituição do ácido hidroxâmico por outros ZBG fornece moléculas ativas frente a células tumorais. Entretanto, a avaliação biológica frente à MMP e HDAC é necessária para confirmar o mecanismo de ação proposto

Inhibition of specific targets such as matrix metalloproteinase (MMP) and histone deacetylase (HDAC) is extensively studied regarding arrest cancer growth. Particularly, concomitant inhibition of MMP and HDAC is effective against solid and hematologic tumors. Both targets have an ion Zn2+ at their catalytic site, which is essential for respective enzymatic activity. High affinity of known MMP and HDAC inhibitors is mainly provided by a potent zinc binding group (ZBG). Hydroxamic acid is the most potent ZBG currently known; however, it presents low pharmacokinetics stability, which results in its ineffectiveness and genotoxicity along clinical trial. So, the aim of this work comprised the design, synthesis, molecular modeling and biological evaluation of novel potential non-hydroxamate dual HDAC/ MMP inhibitors. Compounds were designed by molecular hybridation, employing scaffolds from HDAC and MMP inhibitors, which provided arylsulfonamides with variation about the ZBG type and its respective relative position in the general structure. Seven compounds were synthesized, in two to three reaction steps, through methods that comprise sulfonilation and coupling with condensing agents, using para and meta-aminobenzoic esters as starting material. Compounds showed global yields around 25-55 % and were characterized by 1H and 13C NMR, LC/MS, HPLC and melting point. Compounds were evaluated about their cytotoxicity against HOG (oligodendroma) and T98G (glioblastoma) cells, which 6a, with ZBG 2-aminobenzamide, was the most promising molecules, presenting activity against both cell lines at nM range. Coordination assays with Fe2+ proved the chelating capacity of hydroxamate analogues as well as the cytotoxic compounds, 4a and 4b (ZBG-2, salicylal-hydrazone), which was not observed about 6a. Molecular docking allowed to suggest an interaction model for all proposed ZBG with the respective targets (MMP and HDAC), showing that (ZBG-4) 2-aminobenzamide interacts with HDAC by monodentate way, but does not docks at MMP catalytic site. We conclude that the proposed design allowed obtaining promising compounds as antitumors agents, and the replacement of hydroxamic acid by other ZBG provide active molecules against tumor cells. However, biological evaluation against MMP and HDAC is necessary to confirm the proposed action mechanism

Pharmacokinetics , Genotoxicity , Planning , Chromatography, High Pressure Liquid/methods , Quality Indicators, Health Care/classification , Histone Deacetylase Inhibitors/adverse effects , Matrix Metalloproteinase Inhibitors/adverse effects , Carbon-13 Magnetic Resonance Spectroscopy , Proton Magnetic Resonance Spectroscopy/methods , Neoplasms/pathology
Article in English | LILACS, BBO | ID: biblio-1250451


ABSTRACT Objective: To evaluate genotoxicity of zinc oxide, P. A. calcium hydroxide, mineral trioxide aggregate and an iodoform paste using comet assay on human lymphocytes. Material and Methods: Two positive controls were used: methyl-methanesulfonate for the P.A. calcium hydroxide and mineral trioxide aggregate; and doxorubicin for the iodoform paste and zinc oxide. There were also two negative controls: distilled water for the P.A. calcium hydroxide and mineral trioxide aggregate; and DMSO for the iodoform paste and zinc oxide. Comets were identified using fluorescence microscopy and 100 of them were counted on each of the three slides analyzed per drug test. A damage index was established, taking into consideration the score pattern that had previously been determined from the size and intensity of the comet tail. Analysis of variance, followed by Tukey's test, was used to compare the means of the DNA damage indices. Results: The DNA damage index observed for mineral trioxide aggregate (7.08 to 8.58) and P.A. calcium hydroxide (6.50 to 8.33), which were similar to negative control index. On the other hand, damage index for zinc oxide (104.7 to 218.50) and iodoform paste (115.7 to 210.7) were similar to positive control index. Conclusion: Iodoform paste and zinc oxide showed genotoxicity at all concentrations used.

Humans , Tooth, Deciduous , Zinc Oxide , Comet Assay , Genotoxicity , Mutagenicity Tests/instrumentation , Zinc Oxide , Brazil , Calcium Hydroxide , Analysis of Variance , Microscopy, Fluorescence
Biosci. j. (Online) ; 36(Supplement1): 217-227, Dec. 2020. ilus, tab, graf
Article in English | LILACS | ID: biblio-1355250


Nitrogen accumulation in hydroponically-grown lettuce may pose a health risk to consumers. Thus, the objective of this study was to analyze different concentrations of nitrogen applications in hydroponic lettuce cultivation and their effect on toxicity, cytotoxicity and genotoxicity. A nutrient film technique (NFT) hydroponic system was used to grow the lettuce variety "Vanda." The treatments consisted of different concentrations of nitrogen (in the form of calcium nitrate) in Furlani solution (75, 100, 125 and 150%), a negative and a positive control. The following commercial characteristics were measured: plant fresh weight (PFW), root fresh weight (RFW), shoot fresh weight (SFW), shoot diameter (SD), root dry weight (RDW), shoot dry weight (SDW) and leaf nitrogen (LN). Cytogenotoxicity was indicated by toxicity, cytotoxicity and genotoxicity, which were in turn determined by root length, the mitotic index, chromosomal aberrations and the presence of micronuclei. The nitrogen concentrations used in this experiment did not cause phenotypic toxicity or cytotoxicity in lettuce roots. The most severe genotoxicity was observed at the 125% nitrogen concentration, which nevertheless did not affect commercial characteristics. Although nitrogen fertilization provides great benefits to agriculture, such as greater yields, indiscriminate use should be avoided since concentrations above recommended rates may induce genotoxicity.

O acúmulo de nitrogênio em alface cultivada hidroponicamente pode representar um risco à saúde dos consumidores. Assim, o objetivo deste estudo foi analisar diferentes concentrações de aplicações de nitrogênio no cultivo de alface hidropônica e seus efeitos na toxicidade, citotoxicidade e genotoxicidade. Em sistema hidropônico do tipo filme de nutrientes (NFT) foi usado para cultivar a variedade de alface "Vanda". Os tratamentos consistiram em diferentes concentrações de nitrogênio (na forma de nitrato de cálcio) na solução Furlani (75, 100, 125 e 150%), um controle negativo e um positivo. Foram medidas as seguintes características comerciais: peso fresco da planta (PFW), peso fresco da raiz (RFW), peso fresco da parte aérea (SFW), diâmetro da parte aérea (SD), peso seco da raiz (RDW), peso seco da parte aérea (SDW) e nitrogênio foliar (LN). A citogenotoxicidade foi indicada por toxicidade, citotoxicidade e genotoxicidade, que por sua vez foram determinadas pelo comprimento da raiz, índice mitótico, aberrações cromossômicas e presença de micronúcleos. As concentrações de nitrogênio utilizadas neste experimento não causaram toxicidade fenotípica ou citotoxicidade em raízes de alface. A genotoxicidade mais severa foi observada na concentração de nitrogênio de 125%, que, no entanto, não afetou as características comerciais. Embora a fertilização nitrogenada traga grandes benefícios à agricultura, como maiores rendimentos, o uso indiscriminado deve ser evitado, pois concentrações acima das taxas recomendadas podem induzir genotoxicidade.

Lactuca , Toxicity , Genotoxicity , Nitrogen/analysis
Arq. bras. med. vet. zootec. (Online) ; 72(3): 853-861, May-June, 2020. ilus, tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1129489


The present study tested a comet assay that was modified for compatibility with Giemsa staining to assess the drug genotoxicity in the peripheral blood of rats. We analysed the peripheral blood of 16 female Wistar rats (N=8 rats/group) from a control group and from a group that was treated with an intraperitoneal injection of 50mg cyclophosphamide/kg. The comet assay was carried out with modifications of the blood volume and immersion time in the lysing solution and different combinations of electrophoresis conditions (running time, voltage and current), to Giemsa staining. The lysing time and electrophoresis conditions allowed for the expression of all classes of DNA damage during the electrophoresis run, and the comets were efficiently stained with Giemsa. The technique showed high reproducibility for the DNA classes. The results demonstrate that the modified comet assay with Giemsa staining can be standardized for routine laboratory procedures using a 20µL blood sample, 3h and 30min immersions in the lysing solution and electrophoresis runs with 23 to 25 V and 310 and 360mA of electrical current. The modified comet assay with Giemsa staining that was described in the present study was standardized to be applied in the laboratory routine.(AU)

O presente estudo testou um ensaio cometa modificado para a coloração de Giemsa para avaliar a genotoxicidade de fármacos no sangue periférico de ratos. Analisou-se o sangue periférico de 16 ratas Wistar (n=8 ratas/grupo) de um grupo controle e de um grupo que foi tratado com uma injeção intraperitoneal de 50mg/kg pv. de ciclofosfamida. O ensaio cometa foi realizado com modificações do volume sanguíneo e do tempo de imersão na solução de lise, bem como com diferentes combinações de condições de eletroforese (tempo de corrida, tensão e corrente), para coloração de Giemsa. O tempo de lise e as condições de eletroforese permitiram a expressão de todas as classes de danos no DNA durante a corrida de eletroforese, e os cometas foram eficientemente corados com Giemsa. A técnica mostrou alta reprodutibilidade para as classes de DNA. Os resultados demonstram que o ensaio cometa modificado com coloração de Giemsa foi padronizado para procedimentos laboratoriais de rotina usando-se uma amostra de sangue de 20µL, 3h30min de imersão na solução de lise e eletroforese com 23 a 25 V e 310 e 360mA. O ensaio cometa modificado com coloração de Giemsa descrito foi padronizado para ser aplicado na rotina laboratorial.(AU)

Animals , Rats , Staining and Labeling/veterinary , Azure Stains/toxicity , Comet Assay/veterinary , Genotoxicity/analysis , Electrophoresis/veterinary , Mutagenicity Tests/veterinary
Article in Spanish | LILACS, BDNPAR | ID: biblio-1293084


La tripanosomiasis americana y la leishmaniasis son problemas de salud pública relevantes en Iberoamérica. Las drogas utilizadas actualmente para el tratamiento de estas enfermedades poseen efectos colaterales tóxicos severos. Varios grupos de investigación están abocados a la búsqueda de productos naturales y sintéticos para encontrar nuevos agentes terapéuticos efectivos que no presenten reacciones colaterales adversas. En la evaluación de compuestos de la especie vegetal Zanthoxylum chiloperone (Rutaceae), se demostró que compuestos aislados del extracto presentaban actividad leishmanicida, tripanocida y antifúngica in vivo. Teniendo como antecedentes estos resultados, en el presente estudio se evaluaron los efectos genotóxico y citotóxico del cantín-6-ona y del 5-metoxicantin-6-ona, moléculas aisladas de la planta, en células de médula ósea de animales tratados. El estudio de los efectos genotóxicos se hizo a través del ensayo de modificaciones en la frecuencia de micronúcleos y el efecto citotóxico por modificaciones en la relación entre eritrocitos policromáticos y eritrocitos normocromáticos. Se realizaron 2 ensayos independientes y en cada ensayo los animales fueron divididos en tres grupos de tratamiento: GRUPO I: control negativo que recibió 200 uL de agua y 2.1% de DMSO, vía oral, GRUPO II: compuesto a ser evaluado (canthin-6-ona o 5-methoxicantin-6-ona) con 2.1% de DMSO, y GRUPO III: control positivo que recibió ciclofosfamida 50mg/kg/peso del animal, vía intraperitoneal. El análisis estadístico mostró que ambos compuestos no presentaron efectos genotóxicos ni citotóxicos. Estos resultados permiten proponer a estas moléculas como candidatas a ser sometidas a estudios más detallados como potenciales fármacos contra estas dos enfermedades

American trypanosomiasis and leishmaniasis are relevant public health problems in Latin America. The drugs currently used to treat these diseases have severe toxic side effects. Several research groups are dedicated to the search of natural and synthetic products to find new effective therapeutic agents that do not present adverse collateral reactions. In the evaluation of compounds of the plant species Zanthoxylum chiloperone (Rutaceae), it was shown that isolated compounds of the extract had leishmanicidal, trypanocidal and antifungal in vivo activities. Based on these results, the genotoxic and cytotoxic effects of canthin-6-one and 5-methoxycanthin-6-one, molecules isolated from the plant, on bone marrow cells of treated mice were evaluated in the present study. The study of genotoxic effects was made through the test of modifications in the frequency of micronuclei and the cytotoxic effects by modifications in the relationship between polychromatic erythrocytes and normochromic erythrocytes. Two independent assays were performed and in each assay the animals were divided into three treatment groups: GROUP I: negative control that received 200 µL of water and 2.1% of DMSO, orally, GROUP II: compound to be evaluated (canthin-6 -one or 5-methoxycanthin-6-one) with 2.1% DMSO, and GROUP III: positive control that received cyclophosphamide 50mg /kg animal weight, intraperitoneal. Statistical analysis showed that both compounds had neither genotoxic nor cytotoxic effects. These results allow these molecules to be proposed as candidates to be subjected to more detailed studies as potential drugs against these two diseases

Animals , Mice , Micronucleus Tests , Rutaceae , Animals, Laboratory , Mice , Rats, Inbred Strains , Genotoxicity/adverse effects
J. Health Biol. Sci. (Online) ; 8(1): 1-6, 01/01/2020. ilus
Article in Portuguese | LILACS | ID: biblio-1103689


Objetivo: devido ao consumo rotineiro do café pela população brasileira, o presente trabalho tem como objetivo avaliar o potencial carcinogênico de diferentes concentrações do café (Coffea arabica), por meio do Teste para Detecção de Tumor Epitelial em Drosophila melanogaster. Métodos: para avaliar o efeito carcinogênico do café, larvas de 3° estágio descendentes do cruzamento entre fêmeas virgens wts/TM3, sb¹ e machos mwh/mwh foram tratadas com diferentes concentrações de café comercial (100; 50; 25; 12,5 e 6,26 mg/mL). Após a exposição (48h) e o processo de metamorfose, as moscas adultas foram analisadas quanto à presença de tumor epitelial, e os grupos tratados foram comparados com o controle negativo (água ultrapura). A toxicidade do café foi mensurada por meio da taxa de moscas que sobreviveram a etapa de metamorfose após exposição. Resultados: foi observado diferença estatisticamente significativa na taxa de sobrevivência (p < 0,05) e na frequência de tumor epitelial total (p < 0,05) em moscas tratadas com 100 mg/mL de café, quando comparado ao controle negativo. Conclusões: o café, na concentração de 100 mg/mL, foi tóxico e carcinogênico para D. melanogaster.

Objective: Due to the routine consumption of coffee by the Brazilian population, the present work aims to evaluate the carcinogenic potential of different concentrations of coffee (Coffea arabica) through the Test for Epithelial Tumor Detection in Drosophila melanogaster. Methods: In order to evaluate the carcinogenic effect of coffee, third-stage larvae descended from the cross between virgin females wts/TM3, sb1 and males mwh/mwh were treated with different concentrations of commercial coffee (100, 50, 25, 12, 26 mg/mL). After exposure (48h) and the metamorphosis process, the adult flies were analyzed for the presence of an epithelial tumor and the treated groups were compared with the negative control (ultrapure water). Coffee toxicity was measured by the rate of flies that survived the post-exposure metamorphosis stage. Results: A statistically significant difference was observed in survival rate (p < 0.05) and frequency of total epithelial tumor (p < 0.05) in flies treated with 100 mg/mL of coffee, when compared to the negative control. Conclusions: Coffee at the concentration of 100 mg/mL was toxic and carcinogenic to D. melanogaster.

Genotoxicity , Carcinogenicity Tests , Coffee
Mundo saúde (Impr.) ; 43(2): [390-405], abr., 2019. tab
Article in English, Portuguese | LILACS | ID: biblio-1054507


Amasonia campestris (Aubl.) Moldenke, belongs to the Lamiaceae family, found in the North, Northeast, Midwestand Southeast regions of Brazil. A. campestris tea is popularly used for the fight against malaria, diabetes among otherdiseases. Its common names are mendoca, macaw tail, macaw bamboo. The present study evaluated the genotoxic andantigenotoxic potential of the methanol extract of the roots of Amasonia campestris in polychromatic erythrocytes of Swissmice. The animals were treated with different concentrations of Amasonia campestris (250, 500, 1000 and 2000 mg/kgb.w.) including positive control groups (doxorubicin, DXR 16 mg/kg body weight), negative (water) and solvent (dimethylsulfoxide, DMSO). Concentrations were administered to the animals via a gavage as well as the negative control andsolvent. The positive control was given intraperitoneally. The animals were treated daily with the respective doses for 15days for genotoxic evaluation. after that, samples of caudal peripheral blood were collected at the hours: 24 and 48hrs afterthe first gavage, and on days 7 and 15. For the antigenotoxic evaluation, mice were treated on day 14 with intraperitonealinjections of DXR and caudal peripheral blood samples were collected 24 and 48hrs after this intervention. After thetreatments, 2,000 polychromatic erythrocytes were counted per animal from each group to evaluate the frequency ofMicronuclei. The results showed that the methanol extracts of the roots of A. campestris were not genotoxic because nostatistically significant difference was observed when compared with the negative control. Animals treated with differentconcentrations of Amasonia campestris extracts associated with DXR had a significant reduction of micronucleatedpolychromatic erythrocytes when compared with the positive control. In conclusion, the methan...

Amasonia campestris (Aubl.) Moldenke, pertencente à família Lamiaceae, encontrada nas regiões Norte, Nordeste, Centro-Oeste e Sudeste do Brasil. O chá da A. campestris é utilizado popularmente para o combate à malária, diabetes entreoutras enfermidades. Seu nome popular é mendoca, rabo de arara, bambã de arara. Diante disso, o presente estudoavaliou o potencial genotóxico e antigenotóxico do extrato metanólico das raízes de Amasonia campestris em eritrócitospolicromáticos de camundongos Swiss. Os animais foram tratados com diferentes concentrações da Amasonia campestris(250, 500, 1000 e 2000 mg/kg p.c,) incluindo grupos de controle positivo (doxorrubicina, DXR, 16 mg/kg p.c), negativo(água) e solvente (Dimetilsulfóxido, DMSO). As concentrações foram administradas nos animais via gavagem assimcomo o controle negativo e solvente. O controle positivo foi administrado intraperitonealmente. Os animais receberamtratamento diariamente com as respectivas doses durante 15 dias para avaliação genotóxica, após isso foram coletadasamostras de sangue periférico caudal nas horas: 24 e 48h após a primeira gavagem, e nos dias 7 e 15. Para avaliaçãoantigenotóxica no dia 14 os camundongos foram tratados com injeções intraperitoneal de DXR e foram coletadas amostrasde sangue periférico caudal nas horas: 24 e 48h ao término dessa intervenção. Após os tratamentos, foi feita a contagem de2 mil eritrócitos policromáticos por animal de cada grupo, para avaliação da frequência de Micronúcleos. Os resultados,demonstraram que os extratos metanólicos das raízes da A. campestris não eram genotóxicos, pois não apresentaramdiferença estatisticamente significativa quando comparados ao controle Negativo. Os animais tratados com as diferentesconcentrações do extrato da Amasonia campestris associados a DXR obtiveram uma redução de Eritrócitos PolicromáticosMicronucleados significativa quando comparada ao controle positivo...

Humans , Animals , Antigens , Erythrocytes , Genotoxicity , Toxicity
Rev. peru. med. integr ; 4(1): 4-14, 2019. tab
Article in Spanish | MTYCI, LILACS | ID: biblio-1145755


Objetivos. Determinar la composición química, características físico-químicas y el efecto genotóxico del aceite de Plukenetia volubilis L. Materiales y métodos. Se evaluó el perfil de ácidos grasos, tocoferoles, esteroles, fosfolípidos, carotenoides, tocotrienoles y fenoles; así como las características físico-químicas y trazas metálicas. La genotoxicidad fue evaluada a través del ensayo de morfología de la cabeza de espermatozoides. Para este ensayo, se emplearon ratones albinos machos formando 3 grupos de experimentación de 7 animales cada uno: control negativo (solución salina 0,9%), control positivo (50 mg/kg/pc/día de ciclofosfamida) y grupo problema que recibió por vía oral 0,5 ml de aceite sacha inchi (NIMET); las sustancias se administraron cada 24 horas por 5 días. Resultados. El aceite contiene ácidos grasos poliinsaturados(81,72%), monoinsaturados (10,31%) y saturados(7,67%); siendo el alfa-linolénico (47,35%) y el linoleico (34,34%) los más abundantes. El tocoferol y esterol más abundante fueron el gamma-tocoferol y el beta-siitosterol respectivamente, y en escasa cantidad se halló: fenoles, fosfolípidos, carotenoides y tocotrienoles. Los índices de refracción, saponificación, yodo, peróxido y de acidez, fueron 1,48, 189 mg KOH/g, 190, 0,9 meq/kg, 1,11 KOH/g respectivamente. La densidad, materia insaponificable y humedad y materias volátiles fueron 0,9276, 0,27%, 0,05% respectivamente. Los niveles de arsénico y de plomo, no excedieron los límites máximos permisibles. El grupo de ciclofosfamida mostró una cantidad mayor de espermatozoides anormales (P<0,01) con respecto a los grupos de solución salina y NIMET; no se halló diferencia significativa entre los grupos de solución salina y NIMET . Conclusiones. el aceite de Plukenetia volubilis, es rico en ácidos grasos esenciales alfa-linolénico y linoleico, con una óptima proporción omega 6/omega 3, con significativas cantidades de tocoferoles y fitoesteroles los cuales le brindan una estabilidad oxidativa y con características físico-químicas que corroboran su calidad.En este diseño evaluado el aceite de sacha inchi no induce genotóxicidad, podemos decir que su consumo es seguro como alimento.

Objectives. To determine the chemical composition, physical-chemical characteristics and the genotoxic effect of Plukenetia volubilis L. oil. Materials and methods. The profile of fatty acids, tocopherols, sterols, phospholipids, carotenoids, tocotrienols and phenols was evaluated; as well as the physical-chemical characteristics and metallic traces. Genotoxicity was assessed through the sperm head morphology test. For this test, male albino mice were used forming 3 experimental groups of 7 animals each: negative control (saline solution 0.9%), positive control (50 mg / kg / pc / day of cyclophosphamide) and problem group received via oral 0.5 ml sacha inchi oil (NIMET); the substances were administered every 24 hours for 5 days. Results. The oil contains polyunsaturated (81.72%), monounsaturated (10.31%) and saturated (7.67%) fatty acids; being alpha-linolenic (47.35%) and linoleic (34.34%) the most abundant. The most abundant tocopherol and sterol were gammatocopherol and beta-siitosterol respectively, and in a small amount it was found: phenols, phospholipids, carotenoids and tocotrienols. The indices of refraction, saponification, iodine, peroxide and acidity were 1.48, 189 mg KOH / g, 190, 0.9 meq / kg, 1.11 KOH / g respectively. The density, unsaponifiable matter and moisture and volatile materials were 0.9276, 0.27%, 0.05% respectively. The arsenic and lead levels did not exceed the maximum permissible limits. The cyclophosphamide group showed a higher amount of abnormal sperm (P <0.01) with respect to the saline solution and NIMET groups; no significant difference was found between the saline solution and NIMET groups. Conclusions. Plukenetia volubilis oil, is rich in alphalinolenic and linoleic essential fatty acids, with an optimum omega 6 / omega 3 ratio, with significant amounts of tocopherols and phytosterols which provide oxidative stability and physical-chemical characteristics that corroborate its quality. In this evaluated design sacha inchi oil does not induce genotoxicity, we can say that its consumption is safe as food.

Animals , Male , Mice , Euphorbiaceae/chemistry , Genotoxicity , Plants, Medicinal , Sperm Head , Phytochemicals , Medicine, Traditional
Braz. J. Pharm. Sci. (Online) ; 55: e18217, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011649


The International Agency for Research on Cancer (IARC) placed the most widely used herbicide glyphosate (GLY) into the category 2A (probably carcinogenic to humans), a classification questioned by experts from academia and industry. This article critically appraised the epidemiological and experimental data that led the IARC working group (WG) to consider GLY a probable human carcinogen and the ensuing controversy. An association of GLY with non-Hodgkin lymphoma was suggested by some observational studies. A non-causal explanation for this weak association, however, cannot be excluded. Contrary to WG's view, long-term rodent assays yielded no convincing evidence that GLY is carcinogenic. The mechanistic evidence remains elusive as well. Bacterial reverse mutation tests (including tester strains sensitive to oxidative mutagens) were clearly negative, and so were rodent genotoxicity assays by oral route. Tests with mammalian cells in vitro yielded conflicting results at high (cytotoxic) concentrations of GLY-based formulations. Conflicting results were also obtained when high doses of GLY-based herbicides were administered to rodents by the intraperitoneal route. Such high doses are unlikely to be attained in realistic scenarios of exposure. Finally, the IARC classification is based on a conjectural hazard, and rational public health interventions must be based on estimated risks.

Animals , Male , Female , Mice , Rats , Pesticides/toxicity , Carcinogens/classification , Herbicides/analysis , In Vitro Techniques/instrumentation , Epidemiologic Studies , Genotoxicity/prevention & control
Iatreia ; 31(4): 351-361, oct.-dic. 2018. graf
Article in Spanish | LILACS | ID: biblio-975485


RESUMEN Introducción: en el mundo, el cáncer de próstata es la principal causa de muerte en hombres. Algunas evidencias sugieren que los ácidos grasos omega-3 reducen la viabilidad de las células tumorales mientras que los ácidos omega-6 promueven su proliferación; al respecto, otros estudios han mostrado resultados controvertidos. Objetivo: evaluar los efectos citotóxicos, genotóxicos y anticlonogénicos de ácidos omega-3: α-linolénico (ALA), eicosapentaenoico (EPA) y docosahexaenoico (DHA), omega-6: linoleico (LA), araquidónico (AA) y omega-9: oleico (OA) en células de cáncer de próstata (PC-3). Metodología: se evaluó el efecto sobre la viabilidad celular relativa mediante las pruebas de MTT y Azul de Tripano, el efecto genotóxico mediante intercambios de cromátidas hermanas (ICHs) y ensayo cometa, y el efecto anticlonogénico in vitro, en diferentes concentraciones (25, 50, 100 y 150 µM) de seis ácidos grasos omega en células de cáncer de próstata (PC-3). Resultados: la viabilidad relativa por MTT mostró valores ≤ IC50 con las concentraciones mayores (100 y 150 µM) para los ácidos grasos omega-3 EPA y DHA y omega-6 AA (150 µM), mientras que la viabilidad relativa, evaluada con Azul de Tripano, con estos mismos ácidos, redujeron la viabilidad a 0 %. DHA y EPA mostraron efecto genotóxico y la disminución de la clonogenicidad celular (p < 0,01). Por otro lado, LA y AA disminuyeron la viabilidad relativa observada con Azul de Tripano, sugiriendo diferentes mecanismos de acción de los ácidos grasos en la membrana celular. Conclusión: los resultados mostraron que los ácidos grasos omega-3, EPA, DHA, y omega-6, AA, disminuyen la formación de colonias, reducen la viabilidad celular y aumentan el efecto genotóxico respecto al control no tratado, en el modelo in vitro de células tumorales de próstata PC-3.

SUMMARY Introduction: Prostate cancer is the main cause of cancer related deaths in men worldwide. Previous studies have suggested that omega-3 fatty acids reduce cell viability in tumour cells, whereas omega-6 fatty acids increase clonogenicity. Nevertheless, other reports have shown controversial results. Objective: Evaluate cytotoxicity, genotoxicity and clonogenicity in a prostate cancer derived human cell line (PC-3), treated with fatty acids omega-3: α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA); omega-6: linoleic acid (LA) and arachidonic acid (AA); omega-9: oleic acid (OA). Methods: The tests included (a) cytotoxicity assays by MTT and Trypan Blue; (b) genotoxicity evaluation by the sister-chromatid exchanges technique (SCE) and the DNA-comet assay; and (c) in vitro clonogenic assay of six fatty acids in prostate cancer cell (PC-3) at different concentrations (25 µM, 50 µM, 100 µM and 150 µM). Results: The cell viability by MTT data showed ≤ IC50 values for the omega-3 EPA and DHA and omega-6 AA fatty acids at the two major concentrations (100 µM and 150 µM). Moreover, the same fatty acids viability values dropped to 0 % with Trypan Blue test. EPA and DHA showed genotoxic effect and a clonogenic cell decrease (p<0,01). The latter test also revealed a viability diminishment for LA and AA, suggesting different mechanisms of action of fatty acids on cell membrane. Conclusion: The in vitro evaluation revealed that EPA, DHA and AA reduce the clonogenicity and cell viability of prostate tumour cells and cause genotoxicity in prostate tumour derived PC-3 cells.

Humans , Animals , Prostate , Genotoxicity , Neoplasms
Biomédica (Bogotá) ; 38(4): 467-478, oct.-dic. 2018. tab
Article in Spanish | LILACS | ID: biblio-983956


Introducción. La neumoconiosis de mineros del carbón es una enfermedad crónica e irreversible que se considera un problema de salud pública. Objetivo. Estimar la prevalencia de neumoconiosis y sus factores asociados en mineros de carbón de Boyacá, Cundinamarca y Norte de Santander. Materiales y métodos. Se hizo un estudio de corte transversal en 476 mineros. Se les hizo valoración médica, se tomaron radiografías de tórax siguiendo los criterios de la Organización Internacional del Trabajo, así como espirometrías, y se identificaron los polimorfismos de la glutatión S-transferasa y de las enzimas de reparación. Las asociaciones entre las condiciones ocupacionales y de la empresa con la neumoconiosis, se estudiaron usando modelos de regresión de Cox. Resultados. En 31 empresas se hicieron 479 monitorizaciones ambientales y se evaluaron 476 trabajadores cuyo tiempo de trabajo fluctuaba entre 10 y 57 años. La prevalencia de la neumoconiosis fue de 33,8 % (IC95% 27,0-41,3). En el modelo de regresión multivariado de Cox, con tiempo de riesgo constante para la neumoconiosis, esta se asoció significativamente con el trabajo en empresas medianas (razón de prevalencias, RP=2,00; IC95% 0,995- 2,690; p=0,052), con un nivel alto de exposición al polvo de carbón según el índice de exposición (RP=2,055; IC95% 1,043-4,048; p=0,038), y una antigüedad de 25 años o más (para 25,0 a 29,9 años: RP=2,199; IC95% 1,449-3,338; p=0,001). Conclusiones. La prevalencia de la neumoconiosis fue muy alta y se asoció a la exposición a altos niveles de polvo de carbón, a una exposición laboral mayor o igual a 25 años y al trabajo en empresas medianas.

Introduction: Coal workers' pneumoconiosis is a chronic and irreversible disease representing a public health problem. Objective: To estimate the prevalence of pneumoconiosis and its associated factors among underground coal miners in the Colombian departments of Boyacá, Cundinamarca and Norte de Santander. Materials and methods: We conducted a cross-sectional study of 476 miners to measure the prevalence of pneumoconiosis and its associated factors such as coal dust and silica levels, as well as the occupational conditions. The medical assessment and a chest x-ray were performed according to the International Labor Organization criteria, along with spirometry and the identification of glutathione S-transferase and repair enzyme polymorphisms. The associations were explored using Cox regression models. Results: We performed a total of 479 environmental monitoring sessions in 31 companies and we evaluated 476 workers with 10 to 57 years of mining work experience. The prevalence of pneumoconiosis was 33.8% (95% CI: 27.0 - 41.3%). In the Cox multivariate regression model with a constant risk time, pneumoconiosis was significantly associated with working in medium-sized companies (PR=2.00, 95% CI: 0.995 - 2.690; p=0.052), the level of severe exposure to coal dust (PR=2.055, 95% CI: 1.043 - 4.048; p=0.038), and working in underground mining for 25 years or more (for those with 25.0-29.9 years: PR=2.199, 95% CI: 1.449 - 3.338; p=0.001). Conclusions: The prevalence of pneumoconiosis was very high and was found to be associated with severe exposure to coal dust, work exposure for 25 years or more and working in medium-sized enterprises.

Pneumoconiosis , Coal Mining , Free Silica , Occupational Exposure , Disease Prevention , Genotoxicity