From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC
| العنوان: | From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC |
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| المؤلفون: | Helena Carmo, Félix Carvalho, Maria de Lourdes Bastos, Rita Roque Bravo, Maria João Valente, Diana Silva, João Pedro Silva |
| المصدر: | Archives of Toxicology. 95:1443-1462 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Health, Toxicology and Mutagenesis, medicine.medical_treatment, 010501 environmental sciences, Pharmacology, Toxicology, medicine.disease_cause, 01 natural sciences, Designer Drugs, Methylamines, 03 medical and health sciences, Cell Line, Tumor, Detoxification, Autophagy, medicine, Animals, Humans, Rats, Wistar, Butylone, 3,4-Methylenedioxyamphetamine, 0105 earth and related environmental sciences, Propiophenones, Dose-Response Relationship, Drug, Chemistry, MDMA, Hep G2 Cells, General Medicine, CYP2E1, Butyrophenones, Rats, Stimulant, Oxidative Stress, 030104 developmental biology, Toxicity, Hepatocytes, Chemical and Drug Induced Liver Injury, Oxidative stress, Drug metabolism, medicine.drug |
| الوصف: | Synthetic cathinones are among the most popular new psychoactive substances, being abused for their stimulant properties, which are similar to those of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Considering that the liver is a likely target for cathinones-induced toxicity, and for their metabolic activation/detoxification, we aimed to determine the hepatotoxicity of three commonly abused synthetic cathinones: butylone, α-methylamino-butyrophenone (buphedrone) and 3,4-dimethylmethcathinone (3,4-DMMC). We characterized their cytotoxic profile in primary rat hepatocytes (PRH) and in the HepaRG and HepG2 cell lines. PRH was the most sensitive cell model, showing the lowest EC50 values for all three substances (0.158 mM for 3,4-DMMC; 1.21 mM for butylone; 1.57 mM for buphedrone). Co-exposure of PRH to the synthetic cathinones and CYP450 inhibitors (selective and non-selective) proved that hepatic metabolism reduced the toxicity of buphedrone but increased that of butylone and 3,4-DMMC. All compounds were able to increase oxidative stress, disrupting mitochondrial homeostasis and inducing apoptotic and necrotic features, while also increasing the occurrence of acidic vesicular organelles in PRH, compatible with autophagic activation. In conclusion, butylone, buphedrone and 3,4-DMMC have hepatotoxic potential, and their toxicity lies in the interference with a number of homeostatic processes, while being influenced by their metabolic fate. |
| تدمد: | 1432-0738 0340-5761 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a00fac7766bd2fc48a4f50f88f1f6c1b https://doi.org/10.1007/s00204-021-02990-9 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....a00fac7766bd2fc48a4f50f88f1f6c1b |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14320738 03405761 |
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