title: Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells.
abstract: 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.
authors.affiliation: Laboratório de Neuroquímica e Biologia Celular, Instituto de Ciências da Saúde, Departamento de Biofunção/Bioquímica, Salvador, BA 40.110-100, Brazil.
authors.forename: J P
authors.initials: JP
authors.lastname: Silva-Neto
authors.forename: R A
authors.initials: RA
authors.lastname: Barreto
authors.forename: B P S
authors.initials: BP
authors.lastname: Pitanga
authors.forename: C S
authors.initials: CS
authors.lastname: Souza
authors.forename: V D
authors.initials: VD
authors.lastname: Silva
authors.forename: A R
authors.initials: AR
authors.lastname: Silva
authors.forename: E S
authors.initials: ES
authors.lastname: Velozo
authors.forename: S D
authors.initials: SD
authors.lastname: Cunha
authors.forename: M J M
authors.initials: MJ
authors.lastname: Batatinha
authors.forename: M
authors.initials: M
authors.lastname: Tardy
authors.forename: C S O
authors.initials: CS
authors.lastname: Ribeiro
authors.forename: M F D
authors.initials: MF
authors.lastname: Costa
authors.forename: R S
authors.initials: RS
authors.lastname: El-Bachá
authors.forename: S L
authors.initials: SL
authors.lastname: Costa
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D029864:Crotalaria / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D016686:Monocrotaline / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D009153:Mutagens / Q000302:isolation & purification / Q000378:metabolism / Q000633:toxicity*; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D012639:Seeds / Q000737:chemistry / Q000633:toxicity*; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D009153:Mutagens; D014746:Vimentin; C014114:monocrotaline pyrrole; D016686:Monocrotaline