From street to lab: in vitro hepatotoxicity of buphedrone, butylone and 3,4-DMMC

• Tipo: Artigo em Revista Científica Internacional
• Data: 2021

Autores

Bravo, RR (Autor) Outra; Helena Carmo (Autor) FFUP; Valente, MJ (Autor) Outra; Silva, JP (Autor) Outra; Felix Carvalho (Autor) FFUP; Bastos, MD (Autor) Outra; da Silva, DD (Autor) Outra

Revista

Título: Archives of Toxicology

ISSN: 0340-5761

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-00T-EPT

DOI: 10.1007/s00204-021-02990-9

Abstract (EN): 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, alpha-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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 20