PMID- 11967622 OWN - NLM STAT- MEDLINE DCOM- 20020905 LR - 20131121 IS - 0340-5761 (Print) IS - 0340-5761 (Linking) VI - 76 IP - 3 DP - 2002 Apr TI - Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and liver antioxidant status in mice: influence of ambient temperature. PG - 166-72 AB - The consumption of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is known to cause severe hyperthermia and liver damage in humans. The thermogenic response induced by MDMA is complex and partially determined by the prevailing ambient temperature (AT). This is of extreme importance since ecstasy is often consumed at "rave" parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. In view of the fact that hyperthermia is a well-known pro-oxidant aggressive condition, its potential role in ecstasy-induced hepatocellular toxicity should be further studied. Thus, the present study was performed in order to evaluate the influence of AT on the effects of single administration of MDMA on body temperature and liver toxicity in Charles River mice. Animals were given an acute intraperitoneal dose of MDMA (5, 10 or 20 mg/kg) and placed in AT of 20+/-2 degrees C or 30+/-2 degrees C for 24 h. Body temperature was measured during the study using implanted transponders and a temperature probe reading device. Plasma and liver samples were used for biochemical analysis. Liver sections were also taken for histological examination. The parameters evaluated were (1) plasma levels of transaminases and alkaline phosphatase, (2) hepatic glutathione (GSH), (3) hepatic lipid peroxidation, (4) activity of hepatic antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, glutathione- S-transferase, copper/zinc superoxide dismutase and manganese superoxide dismutase), and (5) liver histology. The hyperthermic response elicited by MDMA was clearly dose-related and potentiated by high AT. Administration of MDMA produced some evidence of oxidative stress, expressed as GSH depletion at both ATs studied, as well as by lipid peroxidation and decreased catalase activity at high AT. High AT, by itself, decreased glutathione peroxidase activity. Histological examination of the liver revealed abnormalities of a dose- and AT-dependent nature. These changes included vacuolation of the hepatocytes, presence of blood clots and loss of typical hepatic cord organisation. The results obtained in the present study suggest that oxidative stress plays a part in the first stage of MDMA-induced liver damage and that liver antioxidant status is aggravated by increased AT. Thus, these findings are in accordance with the hypothesis that high AT may potentiate ecstasy-induced hepatotoxicity by increasing body hyperthermia. FAU - Carvalho, Marcia AU - Carvalho M AD - ICETA/CEQUP, Toxicology Department, Faculty of Pharmacy, University of Porto, Rua Anibal Cunha, 164, 4050-047 Porto, Portugal. marciacarvalho@ff.up.pt FAU - Carvalho, Felix AU - Carvalho F FAU - Remiao, Fernando AU - Remiao F FAU - de Lourdes Pereira, Maria AU - de Lourdes Pereira M FAU - Pires-das-Neves, Ricardo AU - Pires-das-Neves R FAU - de Lourdes Bastos, Maria AU - de Lourdes Bastos M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20020301 PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 0 (Antioxidants) RN - 0 (Hallucinogens) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - EC 3.1.3.1 (Alkaline Phosphatase) RN - GAN16C9B8O (Glutathione) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Alanine Transaminase/blood MH - Alkaline Phosphatase/blood MH - Animals MH - Antioxidants/metabolism MH - Aspartate Aminotransferases/blood MH - Body Temperature/*drug effects MH - Dose-Response Relationship, Drug MH - Glutathione/metabolism MH - Hallucinogens/administration & dosage/*toxicity MH - Injections, Intraperitoneal MH - Lipid Peroxidation/physiology MH - Liver/*drug effects/enzymology/pathology MH - Male MH - Mice MH - Mice, Inbred Strains MH - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity MH - Oxidative Stress/*drug effects/physiology EDAT- 2002/04/23 10:00 MHDA- 2002/09/06 10:01 CRDT- 2002/04/23 10:00 PHST- 2001/10/25 00:00 [received] PHST- 2001/12/20 00:00 [accepted] PHST- 2002/04/23 10:00 [pubmed] PHST- 2002/09/06 10:01 [medline] PHST- 2002/04/23 10:00 [entrez] AID - 10.1007/s00204-002-0324-z [doi] PST - ppublish SO - Arch Toxicol. 2002 Apr;76(3):166-72. doi: 10.1007/s00204-002-0324-z. Epub 2002 Mar 1.