title: Cannabidiol Exposure During Neuronal Differentiation Sensitizes Cells Against Redox-Active Neurotoxins.
abstract: 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 (H2O2). 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.
authors.affiliation: Department of Biochemistry, Laboratory of Cellular Biochemistry, ICBS/UFRGS, Porto Alegre, RS, 90035-003, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Schönhofen
authors.forename: Liana M
authors.initials: LM
authors.lastname: de Medeiros
authors.forename: Ivi Juliana
authors.initials: IJ
authors.lastname: Bristot
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Lopes
authors.forename: Marco A
authors.initials: MA
authors.lastname: De Bastiani
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.forename: José Alexandre S
authors.initials: JA
authors.lastname: Crippa
authors.forename: Mauro Antônio A
authors.initials: MA
authors.lastname: Castro
authors.forename: Richard B
authors.initials: RB
authors.lastname: Parsons
authors.forename: Fábio
authors.initials: F
authors.lastname: Klamt
mesh_terms: D002185:Cannabidiol / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D009498:Neurotoxins; D002185:Cannabidiol; D014212:Tretinoin
references.citation: Curr Med Chem. 2010;17(14):1382-93
references.pmid: 20166926
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jul 3;52:45-52
references.pmid: 24075896
references.citation: Philos Trans R Soc Lond B Biol Sci. 2012 Dec 5;367(1607):3353-63
references.pmid: 23108552
references.citation: J Psychopharmacol. 2013 Jan;27(1):19-27
references.pmid: 23042808
references.citation: Neurobiol Dis. 2005 Jun-Jul;19(1-2):96-107
references.pmid: 15837565
references.citation: Neurochem Res. 2010 Sep;35(9):1323-32
references.pmid: 20514518
references.citation: Diabetes. 2005 Nov;54(11):3274-81
references.pmid: 16249455
references.citation: Anal Biochem. 2009 Feb 1;385(1):107-14
references.pmid: 19027710
references.citation: J Neurosci. 2012 Nov 21;32(47):16651-65
references.pmid: 23175820
references.citation: Trends Pharmacol Sci. 2009 Oct;30(10):515-27
references.pmid: 19729208
references.citation: Prog Neurobiol. 2010 Nov;92(3):370-85
references.pmid: 20624444
references.citation: Ann N Y Acad Sci. 2004 Mar;1012:153-63
references.pmid: 15105262
references.citation: Arch Biochem Biophys. 1959 May;82(1):70-7
references.pmid: 13650640
references.citation: Free Radic Biol Med. 1999 Sep;27(5-6):612-6
references.pmid: 10490282
references.citation: Cell Mol Neurobiol. 2014 Jan;34(1):101-11
references.pmid: 24105026
references.citation: Biol Reprod. 1998 Jun;58(6):1490-5
references.pmid: 9623610
references.citation: Molecules. 2013 Oct 14;18(10):12663-74
references.pmid: 24129275
references.citation: Biol Reprod. 1999 Apr;60(4):839-44
references.pmid: 10084956
references.citation: Neurotoxicology. 2008 May;29(3):520-31
references.pmid: 18417220
references.citation: BMC Res Notes. 2008 Oct 28;1:95
references.pmid: 18957096
references.citation: J Am Chem Soc. 1971 Jan 13;93(1):217-24
references.pmid: 5538858
references.citation: Trends Pharmacol Sci. 2007 Feb;28(2):83-92
references.pmid: 17222464
references.citation: Braz J Psychiatry. 2010 May;32 Suppl 1:S56-66
references.pmid: 20512271
references.citation: Br J Clin Pharmacol. 2013 Feb;75(2):323-33
references.pmid: 22625422
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Neurochem Res. 2008 Dec;33(12):2502-9
references.pmid: 18998208
references.citation: Psychopharmacology (Berl). 2006 Nov;188(4):425-44
references.pmid: 17019571
references.citation: Pharmaceuticals (Basel). 2012 May 21;5(5):529-52
references.pmid: 24281562
references.citation: Bioinformatics. 2004 Feb 12;20(3):307-15
references.pmid: 14960456
references.citation: Pediatr Res. 2008 Dec;64(6):653-8
references.pmid: 18679164
references.citation: Free Radic Biol Med. 1995 Feb;18(2):153-8
references.pmid: 7744297
references.citation: Br J Pharmacol. 2004 May;142(2):231-55
references.pmid: 15155533
references.citation: Neuropharmacology. 2012 Oct;63(5):776-83
references.pmid: 22659086
references.citation: Mol Neurobiol. 2012 Oct;46(2):374-92
references.pmid: 22801993
references.citation: Brain Res. 2010 Aug 12;1348:128-38
references.pmid: 20561509
references.citation: J Anat. 2004 Sep;205(3):213-8
references.pmid: 15379926
references.citation: Chem Biodivers. 2007 Aug;4(8):1678-92
references.pmid: 17712814
references.citation: PLoS One. 2013 May 28;8(5):e63862
references.pmid: 23724009
references.citation: Pediatr Res. 2011 Sep;70(3):272-7
references.pmid: 21654550
references.citation: Free Radic Biol Med. 2008 Jun 1;44(11):1960-9
references.pmid: 18395527
references.citation: Neurotox Res. 2012 Aug;22(2):138-49
references.pmid: 22271527
references.citation: Epilepsy Behav. 2013 Dec;29(3):574-7
references.pmid: 24237632
references.citation: Neurotoxicology. 2012 Jan;33(1):138-46
references.pmid: 22233683
references.citation: J Pharm Pharmacol. 2014 Jun;66(6):844-54
references.pmid: 24392651
references.citation: Braz J Psychiatry. 2008 Sep;30(3):271-80
references.pmid: 18833429
references.citation: Neurotoxicology. 2008 May;29(3):361-76
references.pmid: 18403021
references.citation: FASEB J. 2006 Nov;20(13):2405-7
references.pmid: 17015409
references.citation: Epilepsia. 2001 Oct;42(10):1266-72
references.pmid: 11737161
references.citation: Curr Drug Saf. 2011 Sep 1;6(4):237-49
references.pmid: 22129319
references.citation: Neurochem Int. 2006 Apr;48(5):329-40
references.pmid: 16406146
references.citation: Genome Biol. 2012 Apr 24;13(4):R29
references.pmid: 22531049
references.citation: Neuropathol Appl Neurobiol. 2012 Oct;38(6):535-47
references.pmid: 22236282
references.citation: Cell Commun Signal. 2010 Jun 17;8:12
references.pmid: 20565726
references.citation: Mol Cell Neurosci. 2008 May;38(1):89-97
references.pmid: 18378465
references.citation: Prog Lipid Res. 2013 Oct;52(4):633-50
references.pmid: 24076098
references.citation: Eur J Neurosci. 2007 Aug;26(4):843-51
references.pmid: 17672854
references.citation: Brain Res. 2010 Jun 14;1337:85-94
references.pmid: 20380819
references.citation: Psychopharmacology (Berl). 2012 Feb;219(4):1133-40
references.pmid: 21870037
references.citation: Eur J Pharmacol. 2002 Dec 5;456(1-3):99-106
references.pmid: 12450575
references.citation: PLoS One. 2007 Jul 25;2(7):e641
references.pmid: 17653268
references.citation: Neuropharmacology. 2005 Jun;48(8):1086-96
references.pmid: 15910885
references.citation: Eur J Pharmacol. 1974 Sep;28(1):172-7
references.pmid: 4609777
references.citation: Mol Hum Reprod. 2013 Feb;19(2):93-101
references.pmid: 23112252
references.citation: Eur J Biochem. 2000 May;267(10):2991-7
references.pmid: 10806398
references.citation: Life Sci. 2014 Feb 27;97(1):78-90
references.pmid: 24412391
references.citation: Cytotechnology. 2015 Mar;67(2):299-309
references.pmid: 24493068
references.citation: Mol Neurobiol. 2014 Feb;49(1):222-33
references.pmid: 23893294
references.citation: Cell Biol Int. 2010 Mar 12;34(4):399-408
references.pmid: 19947926
references.citation: ACS Chem Neurosci. 2012 May 16;3(5):400-6
references.pmid: 22860209
references.citation: Exp Eye Res. 2014 Mar;120:175-85
references.pmid: 24495949