Mechanism of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy)‐mediated mitochondrial dysfunction in rat liver
PROTEOMICS September 1, 2008 Kwan–hoon Moon, Vijay Upreti, Li‐rong Yu et al. 62 citations
MDMA (ecstasy) causes liver damage, but the mechanism was poorly understood. In rats, MDMA exposure led to abnormal liver histology, elevated plasma transaminases, nitric oxide synthase, and hydrogen peroxide. Oxidatively modified mitochondrial proteins were labeled with a sensitive probe and identified via mass spectrometry. These included proteins involved in energy supply, fat metabolism, antioxidant defense, and chaperone activities. The activities of mitochondrial aldehyde dehydrogenase, 3-ketoacyl-CoA thiolases, and ATP synthase were significantly inhibited. The data show that MDMA causes oxidative inactivation of key mitochondrial enzymes, likely contributing to mitochondrial dysfunction and subsequent liver damage.