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Titolo:
Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4-methylenedioxymethamphetamine (ecstasy)? An in vitro study using freshly isolated mouse hepatocytes
Autore:
Carvalho, M; Carvalho, F; Bastos, ML;
Indirizzi:
Univ Porto, Fac Pharm, Dept Toxicol, CEQUP, P-4050047 Porto, Portugal UnivPorto Porto Portugal P-4050047 ol, CEQUP, P-4050047 Porto, Portugal
Titolo Testata:
ARCHIVES OF TOXICOLOGY
fascicolo: 12, volume: 74, anno: 2001,
pagine: 789 - 793
SICI:
0340-5761(200102)74:12<789:IHTTFF>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
ISOLATED RAT HEPATOCYTES; MDMA ECSTASY; GLUTATHIONE; METABOLISM;
Keywords:
MDMA; hyperthermia; freshly isolated mouse hepatocytes hepatotoxicity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Carvalho, F Univ Porto, Fac Pharm, Dept Toxicol, CEQUP, Rua Anibal Cunha 164, P-4050047 Porto, Portugal Univ Porto Rua Anibal Cunha 164 Porto Portugal P-4050047 ugal
Citazione:
M. Carvalho et al., "Is hyperthermia the triggering factor for hepatotoxicity induced by 3,4-methylenedioxymethamphetamine (ecstasy)? An in vitro study using freshly isolated mouse hepatocytes", ARCH TOXIC, 74(12), 2001, pp. 789-793

Abstract

The consumption of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) may cause hepatocellular damage in humans, a toxic effect that has been increasing in frequency in the last few years, although the underlying mechanisms are still unknown. The metabolism of MDMA involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites, as is the case with glutathione (GSH). Also, MDMA administration elicits hyperthermia, a potentially deleterious condition that may aggravate its direct toxic effects. Thus, the objective of this study was to evaluate the extentof MDMA-induced depletion of GSH, induction of lipid peroxidation and lossof cell viability in freshly isolated mouse hepatocytes under normothermicconditions (37 degreesC) and to compare the results with the effects obtained under hyperthermic conditions (41 degreesC). By itself, hyperthermia was an important cause of cell toxicity. A rise in incubation temperature from 37 degreesC to 41 degreesC caused oxidative stress in freshly isolated mouse hepatocytes, reflected as a time-dependent induction of lipid peroxidation and consequent loss of cell viability (up to 40-45%), although the variations in GSH and GSSG levels were similar to those under normothermic conditions. MDMA (100, 200, 400, 800 and 1600 muM) induced a concentration- andtime-dependent GSH depletion at 37 degreesC but had a negligible effect onlipid peroxidation and cell viability at this temperature. It is particularly noteworthy that hyperthermia (41 degreesC) potentiated MDMA-induced depletion of GSH, production of lipid peroxidation and loss of cell viability (up to 90-100%). It is therefore concluded that hyperthermia potentiates MDMA-induced toxicity in freshly isolated mouse hepatocytes.

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Documento generato il 25/01/20 alle ore 19:10:39