Mechanism of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy)‐mediated mitochondrial dysfunction in rat liver
Kwan–hoon Moon, Vijay Upreti, Li‐rong Yu, Insong J. Lee, Xiaoying Ye, Natalie D. Eddington, Timothy D. Veenstra, Byoung‐joon Song
PROTEOMICS September 1, 2008 DOI: 10.1002/pmic.200800215 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | MDMA |
| Topics | MDMA |
| Keywords | Mitochondrion Biochemistry Pharmacology Glutathione Mitochondrial toxicity Enzyme |
| Citations | 62 |
| Key points | MDMA causes oxidative inactivation of key mitochondrial enzymes, likely contributing to mitochondrial dysfunction and subsequent liver damage in rats. |
Abstract
Abstract Despite numerous reports citing the acute hepatotoxicity caused by 3,4‐methylenedioxymethamphetamine (MDMA) (ecstasy), the underlying mechanism of organ damage is poorly understood. We hypothesized that key mitochondrial proteins are oxidatively modified and inactivated in MDMA‐exposed tissues. The aim of this study was to identify and investigate the mechanism of inactivation of oxidatively modified mitochondrial proteins, prior to the extensive mitochondrial dysfunction and liver damage following MDMA exposure. MDMA‐treated rats showed abnormal liver histology with significant elevation in plasma transaminases, nitric oxide synthase, and the level of hydrogen peroxide. Oxidatively modified mitochondrial proteins in control and MDMA‐exposed rats were labeled with biotin‐ N ‐maleimide (biotin‐NM) as a sensitive probe for oxidized proteins, purified with streptavidin–agarose, and resolved using 2‐DE. Comparative 2‐DE analysis of biotin‐NM‐labeled proteins revealed markedly increased levels of oxidatively modified proteins following MDMA exposure. Mass spectrometric analysis identified oxidatively modified mitochondrial proteins involved in energy supply, fat metabolism, antioxidant defense, and chaperone activities. Among these, the activities of mitochondrial aldehyde dehydrogenase, 3‐ketoacyl‐CoA thiolases, and ATP synthase were significantly inhibited following MDMA exposure. Our data show for the first time that MDMA causes the oxidative inactivation of key mitochondrial enzymes which most likely contributes to mitochondrial dysfunction and subsequent liver damage in MDMA‐exposed animals.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 13
- Neurotoxicity of Methamphetamine and 3,4-methylenedioxymethamphetamine Life Science July 24, 2013
- The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and d-amphetamine Biological Chemistry January 2, 2011
- Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage Current Pharmaceutical Biotechnology June 27, 2010
- A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) Current Research in Toxicology May 27, 2022
- Recreational MDMA doses do not elicit hepatotoxicity in HepG2 spheroids under normo- and hyperthermia. Toxicology March 1, 2024
and 8 more in the library
Cites 8
- Human Pharmacology of MDMA Therapeutic Drug Monitoring March 19, 2004
- Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices, dosage levels and deaths in the UK (1994–2003) Journal of Psychopharmacology March 30, 2006
- MDMA: A Review of Epidemiological Data Journal of Psychoactive Drugs June 1, 2002
- Synthesis and cytotoxic profile of 3,4-methylenedioxymethamphetamine ("ecstasy") and its metabolites on undifferentiated PC12 cells: A putative structure-toxicity relationship. Chemical Research in Toxicology October 2006
- Serotonergic neurotoxic metabolites of ecstasy identified in rat brain. Journal of Pharmacology and Experimental Therapeutics April 2005
and 3 more in the library