In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells
Autor: | Yigit Sezer, Ayse Tarbin Jannuzzi, Buket Alpertunga, Marilyn A. Huestis |
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Rok vydání: | 2020 |
Předmět: |
Paper
Chemistry Health Toxicology and Mutagenesis medicine.medical_treatment 010401 analytical chemistry Glutathione reductase Neurotoxicity Glutathione JWH-018 Pharmacology Toxicology medicine.disease_cause medicine.disease 01 natural sciences 0104 chemical sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Toxicity medicine Cannabinoid 030217 neurology & neurosurgery Oxidative stress Genotoxicity medicine.drug |
Zdroj: | Toxicol Res (Camb) |
ISSN: | 2045-4538 |
DOI: | 10.1093/toxres/tfaa078 |
Popis: | Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P |
Databáze: | OpenAIRE |
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