Resumo
For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-¹ and 1.0 mg mL-¹ MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-¹). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-¹, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.
Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-¹ e 1,0 mg mL-¹ foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-¹ de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-¹, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.
Assuntos
Aedes , Cebolas/efeitos dos fármacos , Cebolas/genética , Cebolas/toxicidade , Intoxicação por Organofosfatos , MalationResumo
Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.
Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.
Resumo
Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.
Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.
Assuntos
Humanos , Animais , Zika virus , Infecção por Zika virus , Inseticidas/toxicidade , Dano ao DNA , Aberrações Cromossômicas , Raízes de Plantas , Cebolas , Mosquitos Vetores , Malation/toxicidade , Índice MitóticoResumo
For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-¹ and 1.0 mg mL-¹ MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-¹). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-¹, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.(AU)
Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-¹ e 1,0 mg mL-¹ foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-¹ de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-¹, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.(AU)
Assuntos
Cebolas/efeitos dos fármacos , Cebolas/genética , Cebolas/toxicidade , Malation , Aedes , Intoxicação por OrganofosfatosResumo
The study aim was to evaluate the cytotoxic activity, using the MTT test [3-(4,5-Dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide], from the crude extract of Picrasma crenata (Pau Tenente) and its isolated compounds, quassin and parain, in culture of rat liver tumor cells (HTC). The test was carried out exposing the cells for 24, 48 and 72 hours to concentrations of 5, 10, 50, 100, 200, 300, 400, 500 and 1000 µg of crude extract of Pau Tenente/mL of culture medium and 1, 5, 10, 15, 20, 40, 60, 80 and 100 µg of quassin or parain compounds/mL of culture medium. The absorbances averages results obtained showed that the crude extract did not present cytotoxicity for the HTC cells in all the concentrations and evaluated times. For quassin, the concentrations of 80 and 100 µg/mL were cytotoxic, after 72 hours of treatment. For parain, the concentrations of 1, 5, 20, 40, 60, 80 and 100 µg/mL, in 72 hours, were cytotoxic, revealing a new activity for this compound. Thus, the results demonstrate a first indication of the cytotoxic activity of compounds quassin and parain, adding an important social and economic value to them, and may have application in future research and in pharmaceutical industry.
O objetivo do estudo foi avaliar a atividade citotóxica, por meio do teste MTT [brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazólio], do extrato bruto de Picrasma crenata (Pau Tenente) e seus compostos isolados, quassina e paraína, em cultura de células tumorais de fígado de rato (HTC). O teste foi realizado expondo as células por 24, 48 e 72 horas às concentrações de 5, 10, 50, 100, 200, 300, 400, 500 e 1000 µg de extrato bruto de Pau Tenente/mL de meio de cultura e 1, 5, 10, 15, 20, 40, 60, 80 e 100 µg de compostos de quassina ou paraína/mL de meio de cultura. Os resultados das médias de absorbâncias obtidos mostraram que o extrato bruto não apresentou citotoxicidade para as células HTC em todas as concentrações e tempos avaliados. Para quassina, as concentrações de 80 e 100 µg/mL foram citotóxicas, após 72 horas de tratamento. Para a paraína, as concentrações de 1, 5, 20, 40, 60, 80 e 100 µg/mL, em 72 horas, foram citotóxicas, revelando uma nova atividade para este composto. Assim, os resultados demonstram uma primeira indicação da atividade citotóxica dos compostos quassina e paraína, agregando-lhes importante valor social e econômico, podendo ter aplicação em pesquisas futuras e na indústria farmacêutica.
Assuntos
Animais , Ratos , Extratos Vegetais , Picrasma/toxicidade , Quassinas , NeoplasiasResumo
The species Rosmarinus officinalisL. (rosemary) is an herb from the Lamiaceae family, widely used in cooking as a food preservative, seasoning or condiment. It also stands out for its therapeutic properties, mainly presenting antioxidant, antibacterial and antitumor activity. The aim of this study was to evaluate the cytotoxic and mutagenic activity of R. officinalis L. essential oil through the Allium cepabioassay. This test constitutes an excellent plant model routinely used due to its sensitivity, low cost and good correlation with test systems in mammals. The defined concentrations for carrying out the test were 750, 243, 81 and 27 µg mL-1. Five bulbs were used, 4 roots of each, measuring approximately 2 cm, and they were analyzed on two slides. All assays were performed at least in triplicate and compared to the negative control. The statistical test of analysis of variance (ANOVA with a fixed factor) was used, followed by Tukey's multiple comparisons test, for p< 0.05. For this purpose, the GraphPad Prism program (version 6.0) was used. The results showed a cytotoxic and mutagenic effect for all concentrations used of the essential oil of R. officinalisL. However, it is important to conduct further research using other genotoxicological tests with different endpoints and at different concentrations, in order to clarify the interaction of the essential oil of the species R. officinalisL. with the genetic material of the cell and its possible mechanism of action.(AU)
Assuntos
Rosmarinus/genética , Rosmarinus/química , Citotoxinas/análise , Mutagênicos/análise , Bioensaio , Óleos Voláteis/química , CebolasResumo
Infertility is one of the most prevalent health disorders in reproductive-age males and females. Ficus carica (Fc), an herbal plant, has been used traditionally for the treatment of different diseases such as infertility especially in Iranian folk medicine. This study examined the effects of Fc leaf extract on the proliferation of mice spermatogonial stem cells (SSCs). Phenolic, flavonoid content, major polyphenolic compounds and antioxidant activity of the extract was evaluated respectively by Folin-Ciocateu, aluminum chloride, HPLC and the FRAP and DPPH methods. Testicular cells of neonate mice were extracted and their identity was confirmed using cytokeratin for Sertoli and Oct-4, CDHI and PLZF for SSCs. Effects of Fc (0.0875, 0.175, 0.35, 0.71 and 1.42 mg/ml) was evaluated at third, 7th, 9th and 14th days of culture by colony assay. The expression of the Mvh, GFRα1 and Oct-4 genes and the viability and proliferation of cultured cells was assessed at the end of the culture period. The extract has a rich phenolic and flavonoid content such as Rutin, Psoralen, Bergapten and Caffeoylmalic acid using HPLC analysis. It also had a potent reducing and radical scavenging activity. Morphology of colonies was similar in all groups. Higher viability, proliferation, colony number and diameter of SSCs was seen in the presence of Fc leaf extract in a dosedependent manner so that higher number and diameter of colonies were observed in two higher doses of 0.71 and 1.42 mg/ml, separately for each time point relative to other groups. The Mvh, Oct-4 and GFRα1 genes expression had no significant differences between groups. It seems that Fc leaf extract not only had no any cytotoxic effects on the viability and proliferation of SSCs but also support their stemness state. So, this culture system can be employed for enrichment of germ stem cells for use in clinical applications.(AU)
Assuntos
Animais , Camundongos , Extratos Vegetais/efeitos adversos , Ficus/efeitos adversos , Camundongos/embriologia , Citotoxicidade Imunológica , Células-Tronco Germinativas Adultas/citologiaResumo
The present work was designed to investigate the presence of bioactive chemicals in the reaction mixtures (RMs) of peels of Valencia, Mandarin, and African navel oranges, through GC-MS and FT-IR studies. Limonene, a unique compound, is present in the RMs of the three orange peels. Moreover, hexadecanoic acid 2-hydroxy-1-(hydroxymethyl) ethyl ester was identified in the RMs of all the three-orange peels. The RM of Mandarin orange exhibited potent cytotoxic effect against MCF-7 ATCC human breast cancer cells (HBC). All the three RMs exhibited moderate antibacterial activity against the human pathogenic bacteria Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 700603), Salmonella choleraesis (ATCC 10708), Pseudomonas aeruginosa (ATCC 27853), and Proteus mirabilis (ATCC 299).
O presente trabalho almejou investigar a presença de produtos químicos bioativos nas misturas de reação (MRs) de cascas de Valência, Tangerina e laranja umbigo africana, por meio de estudos de GC-MS e FT-IR. Assim, constatou-se que limoneno, um composto único, está presente nos RMs das três cascas de laranja. Além disso, o éster 2-hidroxi1-(hidroximetil) etílico do ácido hexadecanóico foi identificado nos RMs de todas as cascas de três laranjas. A RM da tangerina exibiu potente efeito citotóxico contra células de câncer de mama humano (HBC) MCF-7 ATCC. Todos os três RMs exibiram atividade antibacteriana moderada contra as bactérias patogênicas humanas dos seguintes tipos: Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), Klebsiella pneumoniae (ATCC 700603), Salmonella choleraesis (ATCC 10708), Pseudomonas aeruginosa (ATCC 27853) e Proteus mirabilis (ATCC 299).
Assuntos
Epiderme Vegetal , Citotoxinas/análise , Citrus sinensis , Limoneno/toxicidade , Frutas , Análise EspectralResumo
Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.
Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.
Assuntos
Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/toxicidade , Cebolas/efeitos dos fármacosResumo
Abstract Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.
Resumo Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.
Resumo
Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.(AU)
Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.(AU)
Assuntos
Cebolas/efeitos dos fármacos , Aditivos Alimentares/administração & dosagem , Aditivos Alimentares/toxicidadeResumo
Flavoring additives are of great technological importance for the food industry. However, there is little information regarding the toxicological properties of these micro-ingredients, especially at the cellular level. The present study used meristematic root cells of Allium cepa L. to evaluate the toxicity of a liquid, aroma and flavor synthetic chocolate additive, manufactured and widely marketed throughout Brazil and exported to other countries in South America. The flavoring concentrations evaluated were 100.00; 50.00; 25.00; 1.00; 0.50 and 0.25 µL/L, where the highest concentration established was one-hundred times lower than that commercially suggested for use. The concentration 100 µL/L substantially reduced cell division of meristems within 24- and 48-hours exposure. Concentrations from 100.00 to 0.50 µL/L resulted in a significant number of prophases to the detriment of the other phases of cell division, indicating an aneugenic activity, and induced a significant number of cellular changes, with emphasis on micronuclei, nuclear buds and chromosomal breaks. Under the established analysis conditions, with the exception of concentration 0.25 µL/L, the flavoring of chocolate caused cytotoxicity, genotoxicity and mutagenicity to root meristems.
Os aditivos aromatizantes têm grande importância tecnológica para a indústria de alimentos. Contudo, poucas são as informações quanto as propriedades toxicológicas desses microingredientes, especialmente, em nível celular. No presente estudo avaliou-se, sobre as células meristemáticas de raízes de Allium cepa L., a toxicidade de um aditivo sintético líquido de aroma e sabor de chocolate, fabricado e amplamente comercializado em todo Brasil, e exportado para outros países da América do Sul. As concentrações de aromatizante avaliadas foram 100,00; 50,00; 25,00; 1,00; 0,50 e 0,25 µL/L, onde a maior concentração estabelecida foi cem vezes menor que a sugerida comercialmente para uso. Com base na interpretação dos resultados, a concentração 100 µL/L reduziu substancialmente a divisão celular dos meristemas nas 24 e 48 horas de exposição. As concentrações 100,00 a 0,50 µL/L demonstraram número significativo de prófases em detrimento as outras fases da divisão celular, indicando ação aneugênica, e induziram número significativo de alterações celulares, com ênfase a micronúcleos, broto nucleares e quebras cromossômicas. Nas condições de análises estabelecidas, com exceção a concentração 0,25 µL/L, o aromatizante de chocolate causou citotoxicidade, genotoxicidade e mutagenicidade aos meristemas radiculares.
Assuntos
Chocolate , Mutagênicos/toxicidade , Dano ao DNA , Brasil , Raízes de Plantas , Cebolas , Aditivos AlimentaresResumo
The selective activity of an antineoplastic drug is related to its ability to promote cytotoxic action on tumor cells and preserve the integrity of non-neoplastic cells. Beta-lapachone is extracted from the sawdust of Ipe wood, a thick bark tree from the Ipe wood found in the Brazilian Cerrado biome. This study aimed to evaluate the cytotoxic action of beta-lapachone in an endothelial cell line. The EA.hy926 cells were seeded in two groups, G1 and G2, cultured and exposed to beta-lapachone at concentrations of 0.0, 0.01, 0.03, 0.1, 0.3, 1 and 3 & 956;M for 24 hours. G1 remained under normal cultivation conditions and G2 was subjected to oxidative stress through an ischemia and reperfusion assay, in a deoxygenated sealed chamber. The cytotoxicity assay was performed using the tetrazolium reduction method. In G1, the cytotoxicity ranged from 0.0 to 10.0%; and in G2 between 0.0 and 6.3%. No statistically significant difference was observed between the obtained values. Moreover, we found no cytotoxic action of beta-lapachone on endothelial cells, and the results point out that the drug might have preserved the cells integrity against oxidative stress under the conditions of this experiment. This promising result suggests the possibility of beta-lapachone as a chemotherapy drug with selective activity.
Assuntos
Células Endoteliais/fisiologia , Células Endoteliais/química , Naftoquinonas , Testes Imunológicos de CitotoxicidadeResumo
The selective activity of an antineoplastic drug is related to its ability to promote cytotoxic action on tumor cells and preserve the integrity of non-neoplastic cells. Beta-lapachone is extracted from the sawdust of Ipe wood, a thick bark tree from the Ipe wood found in the Brazilian Cerrado biome. This study aimed to evaluate the cytotoxic action of beta-lapachone in an endothelial cell line. The EA.hy926 cells were seeded in two groups, G1 and G2, cultured and exposed to beta-lapachone at concentrations of 0.0, 0.01, 0.03, 0.1, 0.3, 1 and 3 & 956;M for 24 hours. G1 remained under normal cultivation conditions and G2 was subjected to oxidative stress through an ischemia and reperfusion assay, in a deoxygenated sealed chamber. The cytotoxicity assay was performed using the tetrazolium reduction method. In G1, the cytotoxicity ranged from 0.0 to 10.0%; and in G2 between 0.0 and 6.3%. No statistically significant difference was observed between the obtained values. Moreover, we found no cytotoxic action of beta-lapachone on endothelial cells, and the results point out that the drug might have preserved the cells integrity against oxidative stress under the conditions of this experiment. This promising result suggests the possibility of beta-lapachone as a chemotherapy drug with selective activity.(AU)
Assuntos
Testes Imunológicos de Citotoxicidade , Naftoquinonas , Células Endoteliais/química , Células Endoteliais/fisiologiaResumo
Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.
Assuntos
Asteraceae/citologia , Asteraceae/química , Asteraceae/toxicidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Vitaceae/citologia , Vitaceae/química , Vitaceae/toxicidadeResumo
Cissus verticillata and Sphagneticola trilobata have been used in Brazilian folk medicine for Diabetes Mellitus treatment, although their pharmacological and toxicological profile has not been clearly established. Thus, the aim of this study was to evaluate the preclinical toxicity of the aqueous extracts of C. verticillata and S. trilobata. The main groups of secondary metabolites were investigated, and the species differed by the presence of coumarins in C. verticillata and by tannins in S. trilobata extracts. The highest contents of phenolic compounds and flavonoids were quantified in C. verticillata infusion with 2.594 ± 0.04 mg equivalents of gallic acid g-1 of extract and 1.301 ± 0.015 mg equivalents of catechin g-1 of extract, respectively. While the extract of S. trilobata showed minimum values of these compounds, with 0.002 ± 0.001 mg equivalents of gallic acid g-1 extract and 0.005 ± 0.0004 mg equivalents of catechin g-1 of extract, respectively. These differences implied the results of in vitro antioxidant activity evaluated using ferric reducing antioxidant power (FRAP), in which the sample of C. verticillata at 5 mg mL-1 showed a value of 122 µM ferrous sulfate equivalents (FSE), while S. trilobata showed 0.93 µM FSE at the same concentration. With respect to cytotoxic assay with murine fibroblast cell line (3T3) only S. trilobata exhibited cytotoxic effects measured by MTT and Sulforhodamine B assays, evidenced by the cell viability value of approximately 16%, in both tests after 24 and 72 hours of exposure of the cells to 5 mg mL-1 of the extract. Comparatively, at 5 mg mL-1 the C. verticillata extract showed cell viability of 142% and 95%, respectively, after 24 hours of cell exposure. On the other hand, both species showed genotoxic profiles evidenced by chromosomal aberrations by Allium cepa bioassay, observed by the higher percentage values of chromosome bridges, chromosome loss, and disturbed anaphase for all concentrations of both extracts than those of the negative control. The results support the characterization of the toxicological profile for both species and create an alert regarding the use of S. trilobata, which should be avoided.(AU)
Assuntos
Asteraceae/química , Asteraceae/citologia , Asteraceae/toxicidade , Vitaceae/química , Vitaceae/citologia , Vitaceae/toxicidade , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológicoResumo
Vernonanthura polyanthes, popularly known as assa-peixe, is a medicinal plant that has been widely used by Brazilian Cerrado population for treatment of diseases without a detailed evaluation of their effectiveness, toxicity, and proper dosage. Thus, more studies investigating the safety of V. polyanthes aqueous extract before the use are needed. The purpose of this study was to evaluate the toxicity, cytotoxicity and genotoxicity of V. polyanthes leaves aqueous extract using the Artemia salina and Allium cepa assays. For the A. salina assay, three groups of 10 larvae were exposed to V. polyanthes leaves aqueous extract at the concentrations of 5, 10, 20, 40, and 80 mg/ml. For the A. cepa assay, 5 onion bulbs were exposed to V. polyanthes leaves aqueous extract at 10, 20, and 40 mg/ml, and then submitted to macroscopic and microscopic analysis. As result it was identified a toxicity and cytotoxicity of V. polyanthes dependent on the extract concentration. The A. salina assay suggests that the concentration of 24 mg/ml of the V. polyanthes extract is able to kill 50% of naupllis; while the A. cepa assay suggests that V. polyanthes leaves aqueous extract is toxic at concentrations higher than 20 mg/ml; however the cytotoxic effect in A. cepa root cells was observed at 40 mg/ml of the extract. It is important to say that the V. polyanthes leaves aqueous extract concentration commonly used in popular medicine is 20 mg/ml. Thus, the popular concentration used is very close to toxicity limit in A. salina model (24 mg/ml) and is the concentration which showed toxic effect in A. cepa root cells (20 mg/ml). No genotoxic activity of V. polyantes leaves aqueous extract was observed in the conditions used in this study. Because of the antiproliferative action and no genotoxic activity, V. polyanthes leaves aqueous extract may present compounds with potential use for human medicine. However more detailed studies need to be performed to confirm this potential.(AU)
Vernonanthura polyanthes, popularmente conhecida como assa-peixe, é uma planta medicinal amplamente utilizada pela população brasileira do Cerrado para o tratamento doenças, sem uma avaliação detalhada de sua eficácia, toxicidade e dosagem adequada. Dessa forma, são necessários estudos para investigar a segurança do uso do extrato aquoso de V. polyanthes. O objetivo deste estudo foi avaliar a toxicidade, citotoxicidade e genotoxicidade do extrato aquoso de folhas de V. polyanthes utilizando os ensaios de Artemia salina e Allium cepa. Para o ensaio de A. salina, três grupos de 10 larvas foram expostos ao extrato aquoso de folhas de V. polyanthes nas concentrações de 5, 10, 20, 40 e 80 mg/ml. Para o ensaio de A. cepa, 5 bulbos de cebola foram expostas ao extrato aquoso de folhas de V. polyanthes nas concentrações de 10, 20 e 40 mg/ml, e então submetidos a análise macroscópica e microscópica. O ensaio de A. salina sugere que a concentração de 24 mg/ml do extrato de V. polyanthes é capaz de matar 50% dos náuplios; enquanto o ensaio de A. cepa sugere que o extrato aquoso das folhas de V. polyanthes é tóxico em concentrações superiores a 20 mg/ml. O efeito citotóxico nas células da raiz de A. cepa foi observado apenas na concentração de 40 mg/ml. É importante dizer que a concentração de extrato aquoso de folhas de V. polyanthes comumente usada na medicina popular é de 20 mg/ml. Assim, a concentração popular utilizada está muito próxima do limite de toxicidade no modelo de A. salina (24 mg/ml) e é a mesma concentração que apresentou efeito tóxico nas células da raiz de A. cepa (20 mg/ml). Não foi observada atividade genotóxica do extrato aquoso de folhas de V. polyantes nas condições utilizadas neste trabalho. Por causa da ação antiproliferativa e ausência de atividade genotóxica, o extrato aquoso de folhas de V. polyanthes pode ser uma boa fonte natural de compostos antitumorais e pode apresentar potencial para uso na medicina. No entanto, estudos mais detalhados precisam ser realizados para confirmar esse potencial.(AU)
Assuntos
Vernonia/toxicidade , Plantas Medicinais/toxicidade , Intoxicação por Plantas , Cebolas , ArtemiaResumo
In this study, the toxic effects of melittin on Madin-Darby Bovine Kidney cells (MDBK) were analyzed with respect to mitochondrial functionality by reduction of MTT and flow cytometry, apoptosis potential, necrosis, oxygen reactive species (ROS) production, lipid peroxidation, and DNA fragmentation using flow cytometry and cell membrane destabilization by confocal microscopy. The toxicity presented dose-dependent characteristics and mitochondrial activity was inhibited by up to 78.24 ±3.59% (P<0.01, n = 6) in MDBK cells exposed to melittin (10µg/mL). Flow cytometry analysis revealed that melittin at 2µg/mL had the highest necrosis rate (P<0.05) for the cells. The lipoperoxidation of the membranes was also higher at 2µg/mL of melittin (P<0.05), which was further confirmed by the microphotographs obtained by confocal microscopy. The highest ROS production occurred when the cells were exposed to 2.5µg/mL melittin (P<0.05), and this concentration also increased DNA fragmentation (P<0.05). There was a significative and positive correlation between the lipoperoxidation of membranes with ROS (R=0.4158), mitochondrial functionality (R=0.4149), and apoptosis (R=0.4978). Thus, the oxidative stress generated by melittin culminates in the elevation of intracellular ROS that initiates a cascade of toxic events in MDBK cells.(AU)
Neste estudo, os efeitos tóxicos da melitina em células Madin-Darby Bovine Kidney (MDBK) foram analisados quanto à funcionalidade mitocondrial, por redução de MTT e citometria de fluxo, potencial de apoptose, necrose, produção de espécies reativas de oxigênio (ROS), peroxidação lipídica e fragmentação de DNA, utilizando-se citometria de fluxo e desestabilização da membrana celular, por microscopia confocal. A toxicidade apresentou características dose-dependentes e a atividade mitocondrial foi inibida até 78,24±3,59% (P<0,01, n = 6) em células MDBK expostas à melitina (10µg/mL). Análises por citometria de fluxo revelaram que a melitina a 2µg/mL apresentou o maior índice necrótico celular (P<0,05). A maior lipoperoxidação de membranas também foi na concentração de 2µg/mL de melitina (P<0,05), o que foi posteriormente confirmado por microscopia confocal. A maior produção de ROS aconteceu quando as células foram expostas a 2,5µg/mL de melitina (P<0,05), e essa concentração também aumentou a fragmentação de DNA (P<0,05). Houve uma significativa correlação positiva entre a lipoperoxidação de membranas e a produção de ROS (R=0,4158), funcionalidade mitocondrial (R=0,4149) e apoptose (R=0,4978). Portanto, o estresse oxidativo gerado pela melitina culminou na elevação de ROS intracelular, que inicia uma cascata de eventos tóxicos nas células MDBK.(AU)
Assuntos
Espécies Reativas de Oxigênio/efeitos adversos , Apoptose , Citotoxinas/análise , Meliteno/análise , Venenos de Abelha/análise , Microscopia Confocal , Citometria de FluxoResumo
Hydroxyapatite, chitosan, and carbon nanotube composite biomaterial were developed to improve bone healing. Previous studies suggested that a combination of biomaterials and mesenchymal stem cells (MSCs) can potentially help promote bone regeneration. In the present study, we first developed hydroxyapatite, chitosan, and carbon nanotube composite biomaterial. Then, the effect of different concentrations of the extract on the viability of Vero cells (ATCC CCL-81) and MSCs obtained from sheep bone marrow using methylthiazol tetrazolium (MTT) and propidium iodide (PI) assays were evaluated. The biomaterial group demonstrated an absence of cytotoxicity, similar to the control group. Samples with 50% and 10% biomaterial extract concentrations showed higher cell viability compared to samples from the control group (MTT assay). These results suggest that the presence of this composite biomaterial can be used with MSCs. This study also concluded that hydroxyapatite, chitosan, and carbon nanotube composite biomaterial were not cytotoxic. Therefore, these could be used for performing in vivo tests.(AU)
O compósito à base de hidroxiapatita, quitosana e nanotubo de carbono foi desenvolvido com o intuito de auxiliar na consolidação óssea. Estudos anteriores sugerem que a combinação de substitutos ósseos e células-tronco mesenquimais (CTM) podem auxiliar a potencializar e promover a regeneração óssea. No presente estudo, o biomaterial foi desenvolvido e a viabilidade e a citotoxicidade de células Vero (ATCC CCL-81) e CTM obtidas de medula óssea provenientes de ovinos utilizando ensaios metil-tiazol-tetrazólio, MTT e iodeto de propídeo (PI) foram avaliadas em diferentes concentrações de extrato desse compósito. O compósito demonstrou ausência de citotoxicidade com comportamento semelhante ao grupo controle. Amostras com 50% e 10% de concentração de extrato do compósito mostraram resultados maiores comparados ao grupo controle (ensaio MTT). Esses resultados também sugerem que a presença do biomaterial pode ser utilizada em associação a CTM. Assim, esse estudo conclui que o compósito apresentado de hidroxiapatita, quitosana e nanotubo de cabono não foi considerado citotóxico e pode ser utilizado em teste in vivo.(AU)
Assuntos
Animais , Materiais Biocompatíveis , Durapatita , Quitosana , Citotoxicidade Imunológica , Nanotubos de Carbono , Células-Tronco MesenquimaisResumo
This study evaluated the genotoxicity of lyophilized glycolic extract of Theobroma cacao Linné seeds (TCL), using the micronucleus assay in bone marrow of mice. The interaction between TCL and doxorubicin (DXR) was also analyzed. Experimental groups were evaluated 24-48 h after treatment with N-Nitroso-N-ethylurea (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0.5-2 g/kg), and TCL (2 g/kg) in combination with DXR (antigenotoxic assays). Analysis of micronucleated polychromatic erythrocytes (MNPCEs) showed no significant differences between all the treatment doses of TCL and NaCl control. Mice experimentally treated with DXR and NEU significantly induced MNPCEs. However, a significant reduction of MNPCEs was also observed when TCL was administered in combination with the chemotherapeutic agent DXR. The analysis of the PCE/NCE ratio revealed no significant differences between the NaCl control, all doses of TCL, and DXR. However, there were significant differences in the PCE/NCE ratio between positive NEU control and all other treatments. The PCE/NCE ratio observed after treatment with TCL and DXR showed significant differences and intermediate values to controls (NaCl and NEU). This study suggests absence of genotoxicity and cytotoxicity of TCL, regardless of dose, sex, and time. TCL reduced genotoxic effects induced by DXR, suggesting potential antigenotoxic effects.
Este estudo avaliou a genotoxicidade do extrato glicólico liofilizado de sementes de Theobroma cacao Linné (TCL), usando o ensaio do micronúcleo em medula óssea de camundongos. A interação entre TCL e doxorrubicina (DXR) foi também analisada. Grupos experimentais foram avaliados 24-48 h após tratamento com N-Nitroso-N-etilureia (NEU: 50 mg/kg), DXR (5 mg/kg), NaCl (145 mM), TCL (0,5-2 g/kg), e TCL (2 g/kg) em combinação com DXR (ensaio antigenotóxico). As análises de eritrócitos policromáticos micronucleados (EPCMNs) não mostraram diferenças significantes entre todas as doses de tratamento do TCL e o controle NaCl. Camundongos experimentalmente tratados com DXR e NEU induziram significativamente EPCMNs. Contudo, uma redução significante de EPCMNs foi também observada quando TCL foi administrada em combinação com o agente quimioterapêutico DXR. As análises da relação EPC/ENC (eritrócito policromático/eritrócito normocromático) revelaram ausência de diferenças significantes entre o controle NaCl, todas as doses de TCL e DXR. Contudo, houve diferenças significantes na relação EPC/ENC entre o controle positivo NEU e todos os outros tratamento. A relação ECP/ENC observada após o tratamento com TCL e DXR mostrou diferenças significantes e valores intermediários aos controles (NaCl e NEU). Este estudo sugere ausência de genotoxicidade e citotoxicidade de TCL, independentemente da dose, sexo e tempo. TCL reduziu os efeitos genotóxicos induzidos por DXR, sugerindo potencial efeitos antigenotóxicos.