Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins
Cannabidiol (CBD), one of the most abundant Cannabis sativa -derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD’s neuroprotective effect in terminal diffe...
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Veröffentlicht in: | Molecular neurobiology 2015-08, Vol.52 (1), p.26-37 |
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creator | Schönhofen, Patrícia de Medeiros, Liana M. Bristot, Ivi Juliana Lopes, Fernanda M. De Bastiani, Marco A. Kapczinski, Flávio Crippa, José Alexandre S. Castro, Mauro Antônio A. Parsons, Richard B. Klamt, Fábio |
description | Cannabidiol (CBD), one of the most abundant
Cannabis sativa
-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD’s neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H
2
O
2
). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins. |
doi_str_mv | 10.1007/s12035-014-8843-1 |
format | Article |
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Cannabis sativa
-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD’s neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H
2
O
2
). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-014-8843-1</identifier><identifier>PMID: 25108670</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cannabidiol - chemistry ; Cannabidiol - pharmacology ; Cell Biology ; Cell Differentiation - drug effects ; Cell Line, Tumor ; Cell Shape - drug effects ; Cells ; Gene Expression Regulation - drug effects ; Humans ; Neurobiology ; Neurology ; Neurons - cytology ; Neurons - drug effects ; Neurosciences ; Neurotoxicity ; Neurotoxins - toxicity ; Oxidation-Reduction - drug effects ; Tretinoin - pharmacology</subject><ispartof>Molecular neurobiology, 2015-08, Vol.52 (1), p.26-37</ispartof><rights>Springer Science+Business Media New York 2014</rights><rights>Springer Science+Business Media New York 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c541t-249de32fce4a293310f1d5b324e64211721e3b59510d29bf48134ddec7c963503</citedby><cites>FETCH-LOGICAL-c541t-249de32fce4a293310f1d5b324e64211721e3b59510d29bf48134ddec7c963503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12035-014-8843-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-014-8843-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25108670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schönhofen, Patrícia</creatorcontrib><creatorcontrib>de Medeiros, Liana M.</creatorcontrib><creatorcontrib>Bristot, Ivi Juliana</creatorcontrib><creatorcontrib>Lopes, Fernanda M.</creatorcontrib><creatorcontrib>De Bastiani, Marco A.</creatorcontrib><creatorcontrib>Kapczinski, Flávio</creatorcontrib><creatorcontrib>Crippa, José Alexandre S.</creatorcontrib><creatorcontrib>Castro, Mauro Antônio A.</creatorcontrib><creatorcontrib>Parsons, Richard B.</creatorcontrib><creatorcontrib>Klamt, Fábio</creatorcontrib><title>Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Cannabidiol (CBD), one of the most abundant
Cannabis sativa
-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD’s neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H
2
O
2
). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cannabidiol - chemistry</subject><subject>Cannabidiol - pharmacology</subject><subject>Cell Biology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Shape - drug effects</subject><subject>Cells</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Humans</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurosciences</subject><subject>Neurotoxicity</subject><subject>Neurotoxins - 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Cannabis sativa
-derived compounds, has been implicated with neuroprotective effect in several human pathologies. Until now, no undesired side effects have been associated with CBD. In this study, we evaluated CBD’s neuroprotective effect in terminal differentiation (mature) and during neuronal differentiation (neuronal developmental toxicity model) of the human neuroblastoma SH-SY5Y cell line. A dose-response curve was performed to establish a sublethal dose of CBD with antioxidant activity (2.5 μM). In terminally differentiated SH-SY5Y cells, incubation with 2.5 μM CBD was unable to protect cells against the neurotoxic effect of glycolaldehyde, methylglyoxal, 6-hydroxydopamine, and hydrogen peroxide (H
2
O
2
). Moreover, no difference in antioxidant potential and neurite density was observed. When SH-SY5Y cells undergoing neuronal differentiation were exposed to CBD, no differences in antioxidant potential and neurite density were observed. However, CBD potentiated the neurotoxicity induced by all redox-active drugs tested. Our data indicate that 2.5 μM of CBD, the higher dose tolerated by differentiated SH-SY5Y neuronal cells, does not provide neuroprotection for terminally differentiated cells and shows, for the first time, that exposure of CBD during neuronal differentiation could sensitize immature cells to future challenges with neurotoxins.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>25108670</pmid><doi>10.1007/s12035-014-8843-1</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Biomedical and Life Sciences Biomedicine Cannabidiol - chemistry Cannabidiol - pharmacology Cell Biology Cell Differentiation - drug effects Cell Line, Tumor Cell Shape - drug effects Cells Gene Expression Regulation - drug effects Humans Neurobiology Neurology Neurons - cytology Neurons - drug effects Neurosciences Neurotoxicity Neurotoxins - toxicity Oxidation-Reduction - drug effects Tretinoin - pharmacology |
title | Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins |
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