Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner
العنوان: | Anhydroecgonine methyl ester, a cocaine pyrolysis product, contributes to cocaine-induced rat primary hippocampal neuronal death in a synergistic and time-dependent manner |
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المؤلفون: | Tania Marcourakis, Mariana Sayuri Berto Udo, Silvya Stuchi Maria-Engler, Mariana A. da Silva, Leandro Ferreira Dal'Jovem, Sara de Souza Prates, Stephanie de Oliveira Duro, Fernanda Faião-Flores, Raphael Caio Tamborelli Garcia |
المصدر: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
بيانات النشر: | Springer Science and Business Media LLC, 2021. |
سنة النشر: | 2021 |
مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Hippocampal formation, Pharmacology, Toxicology, Hippocampus, 01 natural sciences, Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, Cocaine, medicine, Animals, 0105 earth and related environmental sciences, Neurons, Chemistry, Vesicle, Autophagy, Neurotoxicity, General Medicine, medicine.disease, Rats, 030104 developmental biology, Apoptosis, Phosphorylation, Neurotoxicity Syndromes, Anhydroecgonine methyl ester, HIPOCAMPO, Pyrolysis |
الوصف: | Crack cocaine users are simultaneously exposed to volatilized cocaine and to its main pyrolysis product, anhydroecgonine methyl ester (AEME). Although the neurotoxic effects of cocaine have been extensively studied, little is known about AEME or its combination. We investigated cell death processes using rat primary hippocampal cells exposed to cocaine (2 mM), AEME (1 mM) and their combination (C + A), after 1, 3, 6 and 12 h. Cocaine increased LC3 I after 6 h and LC3 II after 12 h, but reduced the percentage of cells with acid vesicles, suggesting failure in the autophagic flux, which activated the extrinsic apoptotic pathway after 12 h. AEME neurotoxicity did not involve the autophagic process; rather, it activated caspase-9 after 6 h and caspase-8 after 12 h leading to a high percentage of cells in early apoptosis. C + A progressively reduced the percentage of undamaged cells, starting after 3 h; it activated both apoptotic pathways after 6 h, and was more neurotoxic than cocaine and AEME alone. Also, C + A increased the phosphorylation of p62 after 12 h, but there was little difference in LC3 I or II, and a small percentage of cells with acid vesicles at all time points investigated. In summary, the present study provides new evidence for the neurotoxic mechanism and timing response of each substance alone and in combination, indicating that AEME is more than just a biological marker for crack cocaine consumption, as it may intensify and hasten cocaine neurotoxicity. |
تدمد: | 1432-0738 0340-5761 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d637dfbae4cfa40f9f583c31ce2939e3 https://doi.org/10.1007/s00204-021-03017-z |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....d637dfbae4cfa40f9f583c31ce2939e3 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14320738 03405761 |
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