Juliprosopine and Juliprosine from Prosopis juliflora Leaves Induce Mitochondrial Damage and Cytoplasmic Vacuolation on Cocultured Glial Cells and Neurons

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• 作者：Victor Diogenes A. Silva ; Bruno P. S. Pitanga ; Ravena P. Nascimento ; Cleide S. Souza ; Paulo Lucas C. Coelho ; No茅lio Menezes-Filho ; Andr茅 M谩rio M. Silva ; Maria de F谩tima D. Costa ; Ramon S. El-Bach谩 ; Eudes S. Velozo ; Silvia L. Costa
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：December 16, 2013
• 年：2013
• 卷：26
• 期：12
• 页码：1810-1820
• 全文大小：685K
• 年卷期：v.26,no.12(December 16, 2013)
• ISSN：1520-5010

文摘

Prosopis juliflora is a shrub largely used for animal and human consumption. However, ingestion has been shown to induce intoxication in animals, which is characterized by neuromuscular alterations induced by mechanisms that are not yet well understood. In this study, we investigated the cytotoxicity of a total alkaloid extract (TAE) and one alkaloid fraction (F32) obtained from P. juliflora leaves to rat cortical neurons and glial cells. Nuclear magnetic resonance characterization of F32 showed that this fraction is composed of a mixture of two piperidine alkaloids, juliprosopine (majority constituent) and juliprosine. TAE and F32 at concentrations between 0.3 and 45 渭g/mL were tested for 24 h on neuron/glial cell primary cocultures. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test revealed that TAE and F32 were cytotoxic to cocultures, and their IC₅₀ values were 31.07 and 7.362 渭g/mL, respectively. Exposure to a subtoxic concentration of TAE or F32 (0.3鈥? 渭g/mL) induced vacuolation and disruption of the astrocyte monolayer and neurite network, ultrastructural changes, characterized by formation of double-membrane vacuoles, and mitochondrial damage, associated with changes in 尾-tubulin III and glial fibrillary acidic protein expression. Microglial proliferation was also observed in cultures exposed to TAE or F32, with increasing levels of OX-42-positive cells. Considering that F32 was more cytotoxic than TAE and that F32 reproduced in vitro the main morphologic and ultrastructural changes of 鈥渃ara torta鈥?disease, we can also suggest that piperidine alkaloids juliprosopine and juliprosine are primarily responsible for the neurotoxic damage observed in animals after they have consumed the plant.