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Toxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell lines

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dc.contributor.authorCosta, Joana
dc.contributor.authorBandarra, Susana
dc.contributor.authorSultan, Haider
dc.contributor.authorBell, Suzanne
dc.contributor.authorConstantino Rosa Santos, Susana
dc.contributor.authorQuintas, Alexandre
dc.date.accessioned2019-10-17T11:08:37Z
dc.date.available2019-10-17T11:08:37Z
dc.date.issued2016
dc.description© 2016 Elsevier Ireland Ltd. All rights reserved.pt_PT
dc.description.abstractThe emergence and abuse of synthetic cannabinoids has been increasing as an alternative to cannabis, mainly among youth. As their appearance on the drug market has been recent, the pharmacological and toxicological profiles of these psychoactive substances are poorly understood. Current studies suggest that they have stronger effects compared to their natural alternatives and their metabolites retain affinity towards CB1 receptors in CNS. Since studies on its toxicological properties are scarce, the effects of the drug in human derived cell lines were investigated. The present study was designed to explore the toxicological impact of parent drug versus phase I metabolites of synthetic cannabinoids on human cells with and without CB1 receptor. The human cell line of neuroblastoma SH-SY5Y and human kidney cell line HEK-293T were exposed to JWH-018 and to its N-(3-hydroxypentyl) metabolite. Cell toxicity was evaluated using the MTT and LDH assay. Additionally, a dual staining methodology with fluorescent Annexin V-FITC and propidium iodide was performed to address the question of whether JWH-018 N-(3- hydroxypentyl) metabolite is inducing cell death through apoptosis or necrosis, in HEK293T and SHSY5Y cell lines. The obtained results show that JWH-018 does not cause a statistically significant decrease in cell viability, in contrast to its N-(3-hydroxypentyl) metabolite, which at 25 mM causes a significant decrease in cell viability. Both cell lines are affected by JWH-018 metabolite. Our results point to higher toxicity of JWH-018 metabolite when compared to its parent drug, suggesting a non-CB1 receptor mediated toxicological mechanism. Comparing the results from Annexin V/PI with MTT and LDH assays of SH-SY5Y and HEK293T in the presence of the synthetic cannabinoid metabolite, emerges the picture that cellular viability decreases and associated death is occurring through necrosis.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationForensic Science International 264 (2016) 100–105. Epub 2016 Mar 18.pt_PT
dc.identifier.doi10.1016/j.forsciint.2016.03.024
dc.identifier.issn0379-0738
dc.identifier.urihttp://hdl.handle.net/10451/39873
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/forensic-science-internationalpt_PT
dc.subjectHEK293Tpt_PT
dc.subjectJWH-018pt_PT
dc.subjectJWH-018 N-(3-hydroxypentyl) metabolitept_PT
dc.subjectSH-SY5Ypt_PT
dc.subjectSynthetic cannabinoidspt_PT
dc.subjectToxicitypt_PT
dc.titleToxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell linespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage105pt_PT
oaire.citation.startPage100pt_PT
oaire.citation.titleForensic Science Internationalpt_PT
oaire.citation.volume264pt_PT
person.familyNameMorais Couceiro da Costa
person.familyNameBandarra
person.familyNameSultan
person.familyNameConstantino Rosa Santos
person.familyNameQuintas
person.givenNameJoana
person.givenNameSusana
person.givenNameHaider
person.givenNameSusana
person.givenNameAlexandre
person.identifier1814324
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=kcGK4EYAAAAJ
person.identifier.ciencia-id761F-1AE5-0A17
person.identifier.ciencia-id5411-B5EA-8C71
person.identifier.ciencia-idF11D-8C75-78BF
person.identifier.ciencia-idEF1A-A226-AC0F
person.identifier.orcid0000-0003-2872-7853
person.identifier.orcid0000-0001-9226-6997
person.identifier.orcid0000-0002-2922-0272
person.identifier.orcid0000-0002-5711-1292
person.identifier.orcid0000-0002-5188-0453
person.identifier.ridT-5158-2018
person.identifier.scopus-author-id55943600800
person.identifier.scopus-author-id6701600888
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
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