A mechanistic insight into 3,4-methylenedioxymethamphetamine ("ecstasy")-mediated hepatotoxicity

Abstract

3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a popular drug of abuse among young people with stimulant and hallucinogenic properties. The drug is generally thought to be safe among consumers due to its low-mortality rates. However, MDMA-adverse effects can occur and the risks are not clearly associated to a specific pattern since the consumption quantity seems not to be correlated with the initiation and severity of the injury. MDMA-mediated adverse health effects have been widely studied and can be evoked by multiple factors such as hyperthermia, polydrug abuse (drug-drug interactions), the altered release of neurotransmitters, impairment of mitochondrial function and apoptosis, metabolism and immune responses. Another adverse effect often associated with MDMA is liver toxicity, yet the mechanism of MDMA-induced liver toxicity is not completely understood. A critical starting point appears to be the hepatic metabolism of MDMA by phase I and II enzymes, leading to reactive metabolites. Elucidating the mechanism of hepatic injury mediated by MDMA is of high toxicological and clinical relevance. In this review, an overview of the literature and the latest findings with respect to the mechanism of MDMA-mediated liver toxicity is described.