3,4‐Methylenedioxymethamphetamine (ecstasy)‐induced hepatotoxicity: effect on cytosolic calcium signals in isolated hepatocytes
G. Beitia, A. Cobreros, L. Sainz, E. Cenarruzabeitia
Liver June 1, 1999 DOI: 10.1111/j.1478-3231.1999.tb00041.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro laboratory study Peer reviewed |
|---|---|
| Population | Freshly isolated rat hepatocytes in short-term culture |
| Intervention | MDMA |
| Dose | 0.1–5 mM |
| Duration | 3 h after MDMA incubation |
| Measures | fura-2-acetoxymethylester (fura-2-AM) |
| Topics | MDMA |
| Key points | MDMA produced a sustained rise in cytosolic free calcium in rat hepatocytes, smaller when calcium was absent from the medium, and caused concentration- and time-dependent depletion of GSH and ATP at 0.1 to 5 mM. A non-significant tendency toward increased lipid peroxidation followed GSH loss at three hours. The authors suggest these changes can lead to a rapid decrease in cell viability. |
Abstract
Abstract:Aims/Background: Hepatocellular damage has been reported as a consequence of 3,4‐methylenedioxymethamphetamine (MDMA) intake. 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 Ca2+‐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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 7
- Caffeine and MDMA (ecstasy) exacerbate ER stress triggered by hyperthermia bioRxiv (Cold Spring Harbor Laboratory)
- "Ecstasy"-induced toxicity in SH-SY5Y differentiated cells: role of hyperthermia and metabolites. Archives of Toxicology February 2014
- Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver. Pharmacological Research August 12, 2011
- Cytotoxic effects of 3,4-methylenedioxy-N-alkylamphetamines, MDMA and its analogues, on isolated rat hepatocytes. Archives of Toxicology January 2009
- Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes. Toxicology December 5, 2008
and 2 more in the library
Cites 6
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- Metabolism of methylenedioxymethamphetamine: formation of dihydroxymethamphetamine and a quinone identified as its glutathione adduct. Journal of Pharmacology and Experimental Therapeutics August 1, 1990
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