Cytotoxic effects of amphetamine mixtures in primary hepatocytes are severely aggravated under hyperthermic conditions

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Diana Dias da Silva (Autor) Outra; Elisabete Silva (Autor) Outra; Helena Carrno (Autor) FFUP

Revista

Título: Toxicology in Vitro

Vol. 27 Nº 6

Páginas: 1670-1678

ISSN: 0887-2333

Editora: Elsevier

Indexação

ISI Web of Knowledge - 11 Citações

ISI Web of Science

Scopus - 18 Citações

Pubmed / Medline

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

CORDIS: Ciências da Saúde > Ciências farmacológicas > Toxicologia

Outras Informações

ID Authenticus: P-006-7HD

DOI: 10.1016/j.tiv.2013.04.010

Abstract (EN): Amphetamine consumers are often, deliberately or not, polydrug abusers. Predicting combination effects based on concentration-response analysis of individual components is a valid strategy for accurate toxicological assessment of mixtures. We previously reported that joint effects of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and three other often co-ingested amphetamines (methamphetamine, 4-methylthyoamphetamine and D-amphetamine) could be predicted by the concentration addition (CA) model in HepG2 cells. We sought to further evaluate the relevance of these findings by extending these studies to a cell model that more closely mimics the in vivo situation. Detailed cytotoxic information of the four individual amphetamines on primary rat hepatocytes was recorded by the MTT assay, at 37 degrees C and 40.5 degrees C, simulating the rise in body temperature that could be induced following amphetamine intake. Mixture expectations were calculated using CA and independent action (IA) models. At 37 degrees C, concentration-dependent cytotoxicity occurred for the drugs individually and combined. Mixture effects were accurately predicted by the CA model, while the IA model underestimated cytotoxicity. At 40.5 degrees C these cytotoxic effects were aggravated. Our findings provide evidence of the increased risks associated with the abuse of amphetamine mixtures, especially during hyperthermia, emphasising the need to increase awareness of misinformed users who believe these drugs are safe.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9