Monocrotaline induces acutely cerebrovascular lesions, astrogliosis and neuronal degeneration associated with behavior changes in rats : a model of vascular damage in perspective.
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2023
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Pyrrolizidine alkaloids (PAs) are secondary plant metabolites playing an important role as phytotoxins in the
plant defense mechanisms and can be present as contaminant in the food of humans and animals. The PA
monocrotaline (MCT), one of the major plant derived toxin that affect humans and animals, is present in a high
concentration in Crotalaria spp. (Leguminosae) seeds and can induce toxicity after consumption, characterized
mainly by hepatotoxicity and pneumotoxicity. However, the effects of the ingestion of MCT in the central nervous system (CNS) are still poorly elucidated. Here we investigated the effects of MCT oral acute administration
on the behavior and CNS toxicity in rats. Male adult Wistar were treated with MCT (109 mg/Kg, oral gavage) and
three days later the Elevated Pluz Maze test demonstrated that MCT induced an anxiolytic-like effect, without
changes in novelty habituation and in operational and spatial memory profiles. Histopathology revealed that the
brain of MCT-intoxicated animals presented hyperemic vascular structures in the hippocampus, parahippocampal cortex and neocortex, mild perivascular edema in the neocortex, hemorrhagic focal area in the
brain stem, hemorrhage and edema in the thalamus. MCT also induced neurotoxicity in the cortex and hippocampus, as revealed by Fluoro Jade-B and Cresyl Violet staining, as well astrocyte reactivity, revealed by
immunocytochemistry for glial fibrillary acidic protein. Additionally, it was demonstrated by RT-qPCR that MCT
induced up-regulation on mRNA expression of neuroinflammatory mediator, especially IL1β and CCL2 in the
hippocampus and cortex, and down-regulation on mRNA expression of neurotrophins HGDF and BDNF in the
cortex. Together, these results demonstrate that the ingestion of MCT induces cerebrovascular lesions and
toxicity to neurons that are associated to astroglial cell response and neuroinflammation in the cortex and
hippocampus of rats, highlighting CNS damages after acute intoxication, also putting in perspective it uses as a
model for cerebrovascular damage.
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Monocrotaline, Oral intoxication, Cerebrovascular disorders, Behavioral changes, Astrogliosis
Citação
SILVA, A. L. et al. Monocrotaline induces acutely cerebrovascular lesions, astrogliosis and neuronal degeneration associated with behavior changes in rats: a model of vascular damage in perspective. Neurotoxicology, v. 94, p. 59-70, jan. 2023. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0161813X22001723>. Acesso em: 01 ago. 2023.