Genotoxicity and morphological changes induced by the alkaloid monocrotaline, extracted from Crotalaria retusa, in a model of glial cells

• Published in: Toxicon (Oxford) Vol. 55; no. 1; pp. 105 - 117
• Main Authors: Silva-Neto, J.P., Barreto, R.A., Pitanga, B.P.S., Souza, C.S., Silva, V.D., Silva, A.R., Velozo, E.S., Cunha, S.D., Batatinha, M.J.M., Tardy, M., Ribeiro, C.S.O., Costa, M.F.D., El-Bachá, R.S., Costa, S.L.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 2010; Elsevier
• Subjects: Animal poisons toxicology. Antivenoms; Apoptosis - drug effects; Biological and medical sciences; Cell Line, Tumor; Cell Shape - drug effects; Cell Size - drug effects; Cell Survival - drug effects; Comet Assay; Crotalaria - chemistry; Crotalaria - toxicity; DNA Damage; Dose-Response Relationship, Drug; General pharmacology; Genotoxicity; Glia; Humans; Immunohistochemistry; Medical sciences; Microtubule-Associated Proteins - metabolism; Monocrotaline; Monocrotaline - analogs & derivatives; Monocrotaline - chemical synthesis; Monocrotaline - isolation & purification; Monocrotaline - metabolism; Monocrotaline - toxicity; Mutagens - isolation & purification; Mutagens - metabolism; Mutagens - toxicity; Neuroglia - drug effects; Neuroglia - pathology; Oxidative Stress - drug effects; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant poisons toxicology; Pyrrolizidine alkaloids; Seeds - chemistry; Seeds - toxicity; Time Factors; Toxicology; Vimentin; Vimentin - metabolism; Vimentin; MAPs; Glia; Pyrrolizidine alkaloids; Monocrotaline; Genotoxicity; Glial cell; Toxicity; Neuroglia; Extract; Medicinal plant; Alkaloid; Plant origin; Models
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2009.07.007

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 24
h exposure to 1–500
μM MCT and 500
μM dehydromonocrotaline (DHMC) caused significant increases in cell DNA damage index, which reached 42–64% and 53%, respectively. Cells exposed to 100–500
μM MCT also featured a contracted cytoplasm presenting thin cellular processes and vimentin destabilisation. Conversely, exposure of GL-15 cells to low concentrations of MCT (1–10
μM) clearly induced megalocytosis. Moreover, MCT also induced down regulation of MAPs, especially at the lower concentrations adopted (1–10
μM). Apoptosis was also evidenced in cells treated with 100–500
μM MCT, and a later cytotoxicity was only observed after 6 days of exposure to 500
μM 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.