Historique
Périodique
3,4-methylenedioxymethamphetamine (ecstasy)-induced hepatotoxicity : effect on cytosolic calcium signals in isolated hepatocytes
(Hépatotoxicité liée à l'ecstasy : action sur le calcium cytosolique d' hépatocytes isolés)
Auteur(s) :
BEITIA, G. ;
COBREROS A. ;
SAINZ L. ;
CENARRUZABEITIA E.
Année
1999
Page(s) :
234-241
Langue(s) :
Anglais
ISBN :
0106-9543
Refs biblio. :
38
Domaine :
Drogues illicites / Illicit drugs
Discipline :
PRO (Produits, mode d'action, méthode de dépistage / Substances, action mode, screening methods)
Thésaurus mots-clés
MDMA-ECSTASY
;
FOIE
;
TOXICITE
;
CULTURE DE TISSU
;
MECANISME D'ACTION
;
METABOLISME
;
MODELE ANIMAL
Note générale :
Liver, 1999, 19, 234-241
Résumé :
FRANÇAIS :
On connait peu les mécanismes qui expliquent l'hépatotoxicité de l'ecstasy (MDMA). La réduction du glutathion (GSH), de l'ATP et la peroxidation des lipides sont étudiés en réalisant des cultures d'hépatocytes de rat, incubées en présence de MDMA. L'augmentation du calcium intracellulaire est le résultat le plus remarquable. Parallèllement à la diminution de GSH et d'ATP. Le déficit en GSH est accompagné d'une tendance à l'augmentation de la peroxydation des lipides 3 heures après l'incubation. Ceci suggère que l'augmentation du calcium et la diminution de l'ATP et du GSH peuvent entraîner une perte rapide de la viabilité cellulaire.
ENGLISH :
Aims/Background: Hepatocellular damage has been reported as a consequence of 3,4-methylenedioxymethamphetamine (MDMA) However, little is known about the cellular mechanisms involved. The present study was undertaken to evaluate the effects of MDMA on cell viability as well as free calcium levels ([Ca2+]i) in short-term cultured hepatocytes. Reduced glutathione (GSH), adenosine-5'-triphosphate (ATP) and lipid peroxidation were investigated to evaluate the toxic effect of MDMA, in vitro, using freshly isolated rat hepatocytes. Methods: In order to measure cytosolic free Ca2+ concentrations ([Ca2+]i), rat hepatocytes were loaded with the Ca2+ indicator fura-2-acetoxymethylester (fura 2-AM). Results: A sustained rise of ([Ca2+]i) after incubation with MDMA was the most noteworthy finding. In Ca 2+ -free medium, MDMA caused a reduced increase of ([Ca2+]i). On the other hand, MDMA (0.1-5 mM) induced a concentration-dependent and time exposure-dependent GSH and ATP depletion. Although it did not reach statistical significance, GSH deficits were accompanied by a tendency to increase lipid peroxidation 3 h after MDMA incubation. Conclusions: The above data suggest that the marked rise of ([Ca2+]i) and subsequent ATP and GSH depletion can lead to a rapid decrease in cell viability. (Author's abstract.)
On connait peu les mécanismes qui expliquent l'hépatotoxicité de l'ecstasy (MDMA). La réduction du glutathion (GSH), de l'ATP et la peroxidation des lipides sont étudiés en réalisant des cultures d'hépatocytes de rat, incubées en présence de MDMA. L'augmentation du calcium intracellulaire est le résultat le plus remarquable. Parallèllement à la diminution de GSH et d'ATP. Le déficit en GSH est accompagné d'une tendance à l'augmentation de la peroxydation des lipides 3 heures après l'incubation. Ceci suggère que l'augmentation du calcium et la diminution de l'ATP et du GSH peuvent entraîner une perte rapide de la viabilité cellulaire.
ENGLISH :
Aims/Background: Hepatocellular damage has been reported as a consequence of 3,4-methylenedioxymethamphetamine (MDMA) However, little is known about the cellular mechanisms involved. The present study was undertaken to evaluate the effects of MDMA on cell viability as well as free calcium levels ([Ca2+]i) in short-term cultured hepatocytes. Reduced glutathione (GSH), adenosine-5'-triphosphate (ATP) and lipid peroxidation were investigated to evaluate the toxic effect of MDMA, in vitro, using freshly isolated rat hepatocytes. Methods: In order to measure cytosolic free Ca2+ concentrations ([Ca2+]i), rat hepatocytes were loaded with the Ca2+ indicator fura-2-acetoxymethylester (fura 2-AM). Results: A sustained rise of ([Ca2+]i) after incubation with MDMA was the most noteworthy finding. In Ca 2+ -free medium, MDMA caused a reduced increase of ([Ca2+]i). On the other hand, MDMA (0.1-5 mM) induced a concentration-dependent and time exposure-dependent GSH and ATP depletion. Although it did not reach statistical significance, GSH deficits were accompanied by a tendency to increase lipid peroxidation 3 h after MDMA incubation. Conclusions: The above data suggest that the marked rise of ([Ca2+]i) and subsequent ATP and GSH depletion can lead to a rapid decrease in cell viability. (Author's abstract.)
Affiliation :
Dept Pharmacol., Univ. Navarra, 31008 Pamplona
Espagne. Spain.
Espagne. Spain.