Avaliação de atividades tóxicas, quimioprotetora e quimiopreventiva do extrato nebulizado de cascas de Ximenia americana L. sobre o organismo teste Mus musculus
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Data
2018-09-26
Autores
Dalavilla, Jaqueline Aparecida de Oliveira [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Ximenia americana L., conhecida no popularmente no Brasil como ameixa-do-mato, ameixa-brava ou ameixa-do-sertão. É pertencente a família Olacaceae. Considerando seu uso bem propagado na medicina popular, seus efeitos descritos na literatura e os componentes presentes neste extrato, o presente trabalho avaliou os efeitos do extrato nebulizado das cascas do caule de X. americana L. na toxicidade aguda, subaguda e crônica, bem como seus efeitos ainda não reportados na literatura como potencial citotóxico, mutagênico em células da medula óssea através do ensaio de micronúcleo, sua resposta imunológica em leucócitos circulantes através do ensaio de contagem diferencial de leucócitos e o efeito carcinogênico e/ou anticarcinogênico em câncer colorretal induzido pela 1,2-dimetilhidrazina (DMH) em organismos teste camundongos Mus musculus. Na avaliação da toxicidade aguda de acordo com as orientações do guia OECD 423/2001, nenhuma toxicidade grave ou mortalidade foram observadas nas concentrações de 50, 150, 250, 500 e 2000 mg/kg, classificando o extrato com baixa toxicidade, foi observado uma diminuição significativa na massa relativa dos órgãos como: coração, fígado, pulmão, rins, testículos e tireóide. Estes resultados podem estar relacionados aos constituintes fitoquímicos tais como com potencial pró-oxidantes presentes no extrato como flavonoides, saponinas, antraquinonas, alcaloides, e terpenoides que em altas concentrações podem levar á danos oxidativos. À partir desse estudo foram selecionadas três concentrações para o teste de toxicidade subaguda (150, 250 e 350 mg/kg/dia), de acordo com orientações OECD 407/2008 não foram observados sinais de toxicidade aos animais, tampouco efeito citotóxico ou mutagênico pelo ensaio de micronúcleo em medula óssea de camundongos Mus musculus seguindo o guia OECD 474/2016. A toxicidade crônica do extrato nebulizado de X. americana L. foi avaliada com base no protocolo do guia OECD 452/2009, nas concentrações de 50, 150, 250 e 350 mg/kg, não foi observado sinais de toxicidade ou possível potencial citotóxico e mutagênico de acordo com o guia OECD 474/2016. Na avaliação do efeito quimioprotetor e quimiopreventivo do extrato nebulizado de X. americana L. em células da linhagem branca tais como os leucócitos não demonstraram alterações no processo inflamatório, foi possível observar uma diminuição na formação de FCA (lesões pré-neoplásicas) consideradas como marcadores do câncer de cólon, o extrato testado neste estudo teve uma ação quimioprotetora e quimiopreventiva no câncer colorretal induzido pelo DMH. Acredita-se que esse efeito seja devido aos constituintes fitoquímicos presentes neste extrato, tais como taninos condensados, flavonoides, ácido gálico, epicatequina, catequina, quercetina, liganinas, monoterpenos, sesquiterpenos, diterpenos, naftoquinonas, triterpenos e esteroides, já que muitos desses fitoquímicos são reportados na literatura científica como de ação anticancerígena.
Ximenia americana L., known in the popularly in Brazil as ameixa - do - mato, ameixa - brava or ameixa - do - sertão. It belongs to the family Olacaceae. Considering its well - publicized use in folk medicine, its effects described in the literature and the components present in this extract, the present work evaluated the effects of the nebulized extract of X. americana L. stem bark on acute, subacute and chronic toxicity, as well as its effects not yet reported in the literature as a cytotoxic potential, mutagenic in bone marrow cells through the micronucleus assay, its immune response in circulating leukocytes through the differential leukocyte counting assay, and the carcinogenic and / or anticarcinogenic effect in colorectal cancer induced by 1,2 - dimethylhydrazine (DMH) in test organisms Mus musculus mice. In the acute toxici ty assessment according to the Guideline OECD 423/2001, no serious toxicity or mortality was observed at the concentrations of 50, 150, 250, 500 and 2000 mg / kg, classifying the extract with low toxicity, a significant decrease in the relative mass of organs such as: heart, liver, lung, kidneys, test es and thyroid. These results may be related to the phytochemical constituents such as pro - oxidants present in the extract such as flavonoids, saponins, anthraquinones, alkaloids, and terpenoids that at high concentrations can lead to oxidative damage. Bas ed on this study, three concentrations were selected for the subacute toxicity test (150, 250 and 350 mg / kg / day), according to Guideline OECD 407/2008 no signs of toxicity were observed in the animals, neither cytotoxic nor mutagenic Micronucleus assay in bone marrow of Mus muscul us mice following the Guideline OECD 474/2016. Chronic toxicity of the nebulized X. americana L. extract was evaluated based on the protocol of Guideline OECD 452/2009 at concentrations of 50, 150, 250 and 350 mg / kg, no signs of toxicity or potential cytotoxic potential were observed, and mutagenic according to Guideline OECD 474/2016. In the evaluation of the chemoprotective and chemopreventive effect of X. americana L. nebulized extract in white blood cells such as leukocyte s did not show changes in the inflammatory process, it was possible to observe a decrease in the formation of FCA (pre - neoplastic lesions) considered as markers of the colon cancer, the extract tested in this study had a chemoprotective and chemopreventive action in colorectal cancer induced by DMH. It is believed that this effect is due to phytochemical constituents present in this extract, such as condensed tannins, flavonoids, gallic acid, epicatechin, catechin, quercetin, liganins, monoterpenes, sesquit erpenes, diterpenes, naphthoquinones, triterpenes and steroids, since many of these phytochemicals are reported in the scientific literature as anticancer action.
Ximenia americana L., known in the popularly in Brazil as ameixa - do - mato, ameixa - brava or ameixa - do - sertão. It belongs to the family Olacaceae. Considering its well - publicized use in folk medicine, its effects described in the literature and the components present in this extract, the present work evaluated the effects of the nebulized extract of X. americana L. stem bark on acute, subacute and chronic toxicity, as well as its effects not yet reported in the literature as a cytotoxic potential, mutagenic in bone marrow cells through the micronucleus assay, its immune response in circulating leukocytes through the differential leukocyte counting assay, and the carcinogenic and / or anticarcinogenic effect in colorectal cancer induced by 1,2 - dimethylhydrazine (DMH) in test organisms Mus musculus mice. In the acute toxici ty assessment according to the Guideline OECD 423/2001, no serious toxicity or mortality was observed at the concentrations of 50, 150, 250, 500 and 2000 mg / kg, classifying the extract with low toxicity, a significant decrease in the relative mass of organs such as: heart, liver, lung, kidneys, test es and thyroid. These results may be related to the phytochemical constituents such as pro - oxidants present in the extract such as flavonoids, saponins, anthraquinones, alkaloids, and terpenoids that at high concentrations can lead to oxidative damage. Bas ed on this study, three concentrations were selected for the subacute toxicity test (150, 250 and 350 mg / kg / day), according to Guideline OECD 407/2008 no signs of toxicity were observed in the animals, neither cytotoxic nor mutagenic Micronucleus assay in bone marrow of Mus muscul us mice following the Guideline OECD 474/2016. Chronic toxicity of the nebulized X. americana L. extract was evaluated based on the protocol of Guideline OECD 452/2009 at concentrations of 50, 150, 250 and 350 mg / kg, no signs of toxicity or potential cytotoxic potential were observed, and mutagenic according to Guideline OECD 474/2016. In the evaluation of the chemoprotective and chemopreventive effect of X. americana L. nebulized extract in white blood cells such as leukocyte s did not show changes in the inflammatory process, it was possible to observe a decrease in the formation of FCA (pre - neoplastic lesions) considered as markers of the colon cancer, the extract tested in this study had a chemoprotective and chemopreventive action in colorectal cancer induced by DMH. It is believed that this effect is due to phytochemical constituents present in this extract, such as condensed tannins, flavonoids, gallic acid, epicatechin, catechin, quercetin, liganins, monoterpenes, sesquit erpenes, diterpenes, naphthoquinones, triterpenes and steroids, since many of these phytochemicals are reported in the scientific literature as anticancer action.
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Palavras-chave
Citotoxicidade, Mutagenicidade, Carcinogenicidade, Anticarcinogenicidade, Focos de criptas aberrantes, Toxicidade, Dose letal 50%, Lethal dose 50%, Cytotoxicity, Mutagenicity, Carcinogenicity, Anticarcinogenicity, Foci of aberrant crypts