Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells
Autor: | Silvia Lima Costa, Marcienne Bloch Tardy, Cátia S. Ribeiro, Eudes da Silva Velozo, Cleide dos Santos Souza, Ana Rita da Silva, Maria José Moreira Batatinha, Victor Diogenes Amaral da Silva, Maria de Fátima Dias Costa, S.D. Cunha, R. A. Barreto, Ramon dos Santos El-Bachá, J.P. Silva-Neto, Bruno Penas Seara Pitanga |
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Rok vydání: | 2009 |
Předmět: |
Time Factors
DNA damage Cell Survival Apoptosis Toxicology medicine.disease_cause Cell Line Tumor medicine Humans Vimentin Cell Shape Cell Size Monocrotaline biology Dose-Response Relationship Drug Cell growth Crotalaria biology.organism_classification Molecular biology Immunohistochemistry Comet assay Oxidative Stress medicine.anatomical_structure Biochemistry Cell culture Seeds Neuroglia Comet Assay Microtubule-Associated Proteins Genotoxicity DNA Damage Mutagens |
Zdroj: | Toxicon : official journal of the International Society on Toxinology. 55(1) |
ISSN: | 1879-3150 |
Popis: | Plants of Crotalaria genus (Leguminosae) present large amounts of the pyrrolizidine alkaloid monocrotaline (MCT) and cause intoxication to animals and humans. Therefore, we investigated the MCT-induced cytotoxicity, morphological changes, and oxidative and genotoxic damages to glial cells, using the human glioblastoma cell line GL-15 as a model. The comet test showed that 24h exposure to 1-500microM MCT and 500microM dehydromonocrotaline (DHMC) caused significant increases in cell DNA damage index, which reached 42-64% and 53%, respectively. Cells exposed to 100-500microM MCT also featured a contracted cytoplasm presenting thin cellular processes and vimentin destabilisation. Conversely, exposure of GL-15 cells to low concentrations of MCT (1-10microM) clearly induced megalocytosis. Moreover, MCT also induced down regulation of MAPs, especially at the lower concentrations adopted (1-10microM). Apoptosis was also evidenced in cells treated with 100-500microM MCT, and a later cytotoxicity was only observed after 6 days of exposure to 500microM MCT. The data obtained provide support for heterogenic and multipotential effects of MCT on GL-15 cells, either interfering on cell growth and cytoskeletal protein expression, or inducing DNA damage and apoptosis and suggest that the response of glial cells to this alkaloid might be related to the neurological signs observed after Crotalaria intoxication. |
Databáze: | OpenAIRE |
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