Abstract |
Abuse of synthetic drugs is widespread worldwide. Studies indicate that piperazine designer drugs act as substrates at dopaminergic and serotonergic receptors and/or transporters in the brain. This work aimed to investigate the cytotoxicity of N-benzylpiperazine, 1-(3-trifluoromethylphenyl)piperazine, 1-(4-methoxyphenyl)piperazine and 1-(3,4-methylenedioxybenzyl)piperazine in the differentiated human neuroblastoma SH-SY5Y cell line. Cytotoxicity was evaluated after 24 h incubations through the MTT reduction and neutral red uptake assays. Oxidative stress (reactive oxygen and nitrogen species production and glutathione content) and energetic ( ATP content) parameters, as well as intracellular Ca(2+), mitochondrial membrane potential, DNA damage (comet assay) and cell death mode were also evaluated. Complete cytotoxicity curves were obtained after 24 h incubations with each drug. A significant decrease in intracellular total glutathione content was noted for all the tested drugs. All drugs caused a significant increase of intracellular free Ca(2+) levels, accompanied by mitochondrial hyperpolarization. However, ATP levels remained unchanged. The investigation of cell death mode revealed a predominance of early apoptotic cells. No genotoxicity was found in the comet assay. Among the tested drugs, 1-(3-trifluoromethylphenyl)piperazine was the most cytotoxic. Overall, piperazine designer drugs are potentially neurotoxic, supporting concerns on risks associated with the abuse of these drugs.
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Authors | M D Arbo, R Silva, D J Barbosa, D Dias da Silva, S P Silva, J P Teixeira, M L Bastos, H Carmo |
Journal | Journal of applied toxicology : JAT
(J Appl Toxicol)
Vol. 36
Issue 1
Pg. 121-30
(Jan 2016)
ISSN: 1099-1263 [Electronic] England |
PMID | 25900438
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 John Wiley & Sons, Ltd. |
Chemical References |
- Designer Drugs
- Piperazines
- Piperazine
- Glutathione
- Calcium
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Topics |
- Apoptosis
(drug effects)
- Calcium
(metabolism)
- Cell Line, Tumor
- Designer Drugs
(toxicity)
- Glutathione
(metabolism)
- Humans
- In Vitro Techniques
- Membrane Potential, Mitochondrial
(drug effects)
- Mitochondria
(drug effects)
- Neuroblastoma
(pathology)
- Neurotoxicity Syndromes
(etiology)
- Piperazine
- Piperazines
(toxicity)
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