Cardiac oxidative stress determination and myocardial morphology after a single ecstasy (MDMA) administration in a rat model

Abstract

Experimental and clinical data indicate that 3,4-methylenedioxy-N-methylamphetamine (MDMA) abuse can produce significant cardiovascular toxicity. A mechanism may be a direct toxic effect of redox active metabolites of MDMA. To evaluate the effect of a single MDMA dose on cellular antioxidant defence system and to investigate the morphology in male albino rats, total glutathione (GSH), oxidised glutathione (GSSG), ascorbic acid (AA), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and malondialdehyde (MDAL) were studied. The effects were evaluated at 3, 6, 16 and 24 h after MDMA administration. Antioxidant enzymes activity was significantly reduced: GPx (-24%) and SOD (-50%) after 3 h and GR (-19%) after 6 h from treatment. AA levels decrease (-37%) after 3 h and (-30%) after 6 h; MDAL level increased (+119%) after 3 h; GSH levels decreased after 3 (31.3%) and 6 h (37.9%) from MDMA treatment. GSSG content was not affected by ecstasy administration. Myocardial contraction band necrosis (CBN) was already visible in rats killed at 6 h. After 16 h, macrophagic monocytes around the necrotic myocardial cells were observed, and within 24 h, this infiltrate became more widespread with an early removal of the necrotic material. Calcium deposits were observed within ventricular cardiomyocytes with intact nuclei and sarcomeres. Single administration of MDMA can significantly alter the cellular antioxidant defence system and produce oxidative stress which may result in lipid peroxidation and disruption of Ca(2 +) homeostasis. The depression in Ca(2+) regulatory mechanism by reactive oxygen species ultimately results in intracellular Ca(2 +) overload, CBN and cell death.

Enzymatic–nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity

“…This study demonstrates that the administration of a single dose of MDMA (20 mg/kg ip) was able to alter significantly the antioxidant defense system, producing an oxidative stress that may result in lipid peroxidation, with consequent deterioration of the homeostasis of Ca 2+ and neuronal damage. Numerous mechanisms have been suggested to be responsible for MDMA toxicity, such as oxidative stress, metabolic compromise, and inflammation (Cerretani et al, 2008). The role of oxidative stress in mediating MDMA toxicity is further illustrated by a decrease in the activity of the endogenous antioxidants gluthatione peroxidase, catalase, and superoxide dismutase observed after MDMA administration (Yamamoto and Raudensky, 2008).…”

Insight into stress-induced cardiomyopathy and sudden cardiac death due to stress. A forensic cardio-pathologist point of view

“…Exposure of normal myocardium to ROS-generating systems alters myocardial function through persistent cellular loss of K+, depletion of high-energy phosphates, elevated intracellular calcium concentration, loss of systolic force development, progressive diastolic tension, and depressed metabolic function [20,21]. Catecholamines may induce oxidative damage through reactive intermediates resulting from their auto-oxidation, irrespective of their interaction with adrenergic receptors, thus representing an important factor in the pathogenesis of catecholamines induced cardiotoxicity [22]. In a previous paper we have described the effect of ROS on the catecholamine-mediated myocardial expressions of TNF-a (tumor necrosis factor-alpha), MCP-1 (monocyte chemotactic protein-1), interleukins IL6, IL8, IL10 and a significant apoptotic process randomly sparse in the damaged myocardium [21].…”

Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

“…Certain drugs such as the antibreast cancer agent tamoxifen and antiretroviral drugs including AZT (zidovudine) can promote fatty liver disease ([12], and references herein). Likewise, abused substances such as marijuana (cannabinoids), nicotine (a major component of tobacco smoke), and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) can lead to hepatic steatosis and inflammation (steatohepatitis) [13–15] as well as tissue injury in extrahepatic organs including brain and heart [16–19]. …”