Investigação de potencial genotóxico e clastogênico/aneugênico do extrato de frutos de Crataegus oxyacantha: análises in vitro
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Data
2016-07-19
Autores
Quadros, Ana Paula Oliveira de [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Cerca de 11% dos medicamentos considerados essenciais pela OMS são derivados de plantas medicinais, daí a importância do desenvolvimento de testes científicos sobre essas plantas, avaliando, além do seu real potencial farmacológico, a genotoxicidade, mutagenicidade, antigenotoxicidade, citotoxicidade, dentre outros, para esclarecer se o uso de tais plantas por seres humanos é seguro. Crataegus oxyacantha é uma planta originalmente encontrada na Europa e, devido à suas potencialidades medicinais, já há muito tempo foi introduzida no continente sulamericano. Pertencente à família Rosaceae, a árvore forma, na primavera, cachos grandes de flores brancas ou rosas de fragrância agradável, que no outono se transformam em pequenos frutos vermelhos. A importância da C. oxyacantha se dá pela presença comprovada de flavonóides, que são conhecidos por sua ação antioxidante. Devido a inexistência na literatura de estudos investigando a toxicidade genética de C. oxyacantha para os seres humanos, o presente estudo foi elaborado visando avaliar se o extrato de frutos desta planta apresenta efeitos citotóxico, genotóxico e clastogênico/aneugênico em leucócitos humanos e células HepG2 em cultura, e mutagênico em cepas de Salmonella typhimurium (teste de Ames). Os resultados da análise de genotoxicidade mostraram que o extrato não apresentou efeitos genotóxicos nas concentrações de 2,5 e 5,0 µg/ml em ambos os tipos celulares analisados, no entanto, em concentrações acima de 10 µg/ml verificou-se a ocorrência de danos significativos ao DNA. Os resultados do teste do micronúcleo também mostraram que nas concentrações de 10µg/ml e superiores foram observados efeitos mutagênicos nas células estudadas. No teste de Ames, somente na cepa TA98 de S. typhimurium, com ativação metabólica, o extrato se mostrou mutagênico. Os dados obtidos no presente estudo nos permitem concluir que, nas condições do experimento, o extrato de frutos de C. oxyacantha apresenta efeito genotóxico e clastogênico/aneugênico em concentrações acima de 10 µg/ml; e pelo teste de Ames, o extrato, após metabolização, apresenta efeitos mutagênicos. Devido ao potencial medicinal desta planta e ao fato de algumas formulações com extratos da mesma já estarem sendo comercializados, os resultados de genotoxicidade positiva obtidos neste trabalho indicam cautela no uso desse extrato, e apontam para a necessidade de mais estudos, tanto in vitro quanto in vivo, que avaliem a toxicidade genética do extrato de frutos e de outras partes desta planta.
About 11% of medicines considered essential by WHO are derived from medicinal plants, being important to develop scientific tests on these plants, evaluating several aspects as its pharmacological potential, genotoxicity, mutagenicity, antigenotoxicity, cytotoxicity, among others, to clarify if the use of such plants is safe for humans. Crataegus oxyacantha is a plant originally found in Europe and due to its medicinal potential, was at long time introduced in the South American continent. Belonging to the Rosaceae family, the tree form in the spring, large bunches of white flowers and pleasant fragrance of roses, which in autumn turn into small red fruits. The importance of C. oxyacantha is attributed to the presence of flavonoids as constituents, which are known for their antioxidant activity. Considering the absence in the literature of studies investigating the genetic toxicity of C. oxyacantha to humans, this study was designed to evaluate if the fruits extract of this plant present a cytotoxic, genotoxic and clastogenic/aneugenic effects in cultured human HepG2 and leukocytes cells, and mutagenicity in Salmonella typhimurium strains (Ames test). The results of genotoxicity analysis evidenced that the extract showed no genotoxic effects at 2.5 and 5.0 ug/ml concentrations, in both cell types tested, however, at concentrations above of 10 ug/ml significant DNA damage was observed. The micronucleus test results showed that the concentrations above of 10 ug/ml also produced clastogenic/aneugenic effects on the cells studied. The Ames test showed that in the S. typhimurium TA98 strain, with metabolic activation of the extract, was observed mutagenic effects. The data obtained in this study allow us to conclude that, under the experimental conditions employed, the fruits extract of C. oxyacantha has genotoxic and clastogenic/aneugenic effects at concentrations above of 10 ug/ml; and by the Ames test, the extract after metabolization, has mutagenic effects. Due to the medical potential of this plant and the fact that some formulations with extracts of it are already being marketed, the genetic toxicity observed in this study indicate caution in the use of this extract, and point to the necessity of further studies, both in vitro and in vivo, to better evaluate the genotoxicity of the fruit extract and other parts of this plant.
About 11% of medicines considered essential by WHO are derived from medicinal plants, being important to develop scientific tests on these plants, evaluating several aspects as its pharmacological potential, genotoxicity, mutagenicity, antigenotoxicity, cytotoxicity, among others, to clarify if the use of such plants is safe for humans. Crataegus oxyacantha is a plant originally found in Europe and due to its medicinal potential, was at long time introduced in the South American continent. Belonging to the Rosaceae family, the tree form in the spring, large bunches of white flowers and pleasant fragrance of roses, which in autumn turn into small red fruits. The importance of C. oxyacantha is attributed to the presence of flavonoids as constituents, which are known for their antioxidant activity. Considering the absence in the literature of studies investigating the genetic toxicity of C. oxyacantha to humans, this study was designed to evaluate if the fruits extract of this plant present a cytotoxic, genotoxic and clastogenic/aneugenic effects in cultured human HepG2 and leukocytes cells, and mutagenicity in Salmonella typhimurium strains (Ames test). The results of genotoxicity analysis evidenced that the extract showed no genotoxic effects at 2.5 and 5.0 ug/ml concentrations, in both cell types tested, however, at concentrations above of 10 ug/ml significant DNA damage was observed. The micronucleus test results showed that the concentrations above of 10 ug/ml also produced clastogenic/aneugenic effects on the cells studied. The Ames test showed that in the S. typhimurium TA98 strain, with metabolic activation of the extract, was observed mutagenic effects. The data obtained in this study allow us to conclude that, under the experimental conditions employed, the fruits extract of C. oxyacantha has genotoxic and clastogenic/aneugenic effects at concentrations above of 10 ug/ml; and by the Ames test, the extract after metabolization, has mutagenic effects. Due to the medical potential of this plant and the fact that some formulations with extracts of it are already being marketed, the genetic toxicity observed in this study indicate caution in the use of this extract, and point to the necessity of further studies, both in vitro and in vivo, to better evaluate the genotoxicity of the fruit extract and other parts of this plant.
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Palavras-chave
Crataegus oxyacantha, Ensaio cometa, Mutagênese, Teste de ames, Teste do micronúcleo