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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Diana Dias da Silva (Author) Other; Elisabete Silva (Author) Other; Helena Carrno (Author) FFUP

Journal

Title: Toxicology in Vitro

Vol. 27 No. 6

Pages: 1670-1678

ISSN: 0887-2333

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 11 Citations

ISI Web of Science

Scopus - 18 Citations

Pubmed / Medline

Scientific classification

FOS: Medical and Health sciences > Basic medicine

CORDIS: Health sciences > Pharmacological sciences > Toicology

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9