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Eduarda Fernandes

26 papers in the library · 268 citations · publishing 2002-2022

Papers

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Ecstasy metabolites and monoamine neurotransmitters upshift the Na+/K+ ATPase activity in mouse brain synaptosomes.

Archives of Toxicology December 2022 Daniel José Barbosa, João Paulo Capela, Luísa Maria Ferreira et al.

3,4-Methylenedioximethamphetamine (MDMA; "ecstasy") is a psychotropic drug with well-known neurotoxic effects mediated by hitherto not fully understood mechanisms. The Na+- and K+-activated adenosine 5'-triphosphatase (Na+/K+ ATPase), by maintaining the ion gradient across the cell membrane, regulates neuronal excitability. Thus, a perturbation of its function strongly impacts cell homeostasis,...

DOI: 10.1007/s00204-022-03370-7 (opens in new tab) Full text (opens in new tab) 3,4-Methylenedioxymethamphetamine MDMA MDMA Brain Effects MDMA Metabolites Monoamine neurotransmitters +2

GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA).

Archives of Toxicology November 2018 Ana Margarida Araújo, Maria de Lourdes Bastos, Eduarda Fernandes et al.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a well-known hepatotoxic drug. Although its toxicity has been thoroughly studied at high concentrations, there is still insufficient knowledge on possible alterations of cell function at subtoxic concentrations, which are in fact more representative concentrations of intoxication scenarios. In this study, a gas chromatography-mass...

DOI: 10.1007/s00204-018-2314-9 (opens in new tab) Full text (opens in new tab) MDMA Hepatotoxicity Metabolomics Primary mouse hepatocytes +1

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

Archives of Toxicology July 2018 R Feio-Azevedo, V M Costa, D J Barbosa et al.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats...

DOI: 10.1007/s00204-018-2226-8 (opens in new tab) Full text (opens in new tab) Aged rats Cardiotoxicity Nephrotoxicity Neurotoxicity +2

Hyperthermia Severely Affects the Vascular Effects of MDMA and Metabolites in the Human Internal Mammary Artery In Vitro.

Cardiovascular toxicology October 2017 D A Fonseca, A F Guerra, F Carvalho et al.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a recreational drug used worldwide for its distinctive psychotropic effects. Although important cardiovascular effects, such as increased blood pressure and heart rate, have also been described, the vascular effects of MDMA and metabolites and their correlation with hyperthermia (major side effect of MDMA) are not yet fully understood and...

DOI: 10.1007/s12012-017-9398-y (opens in new tab) Full text (opens in new tab) MDMA 3,4-methylenedioxymethamphetamine 5-hydroxytryptamine Hyperthermia +1

Effects of 3,4-methylenedioxymethamphetamine administration on retinal physiology in the rat.

PLoS One June 14, 2016 João Martins, Miguel Castelo-Branco, Ana Batista et al. 10 citations

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy) is known to produce euphoric states, but may also cause adverse consequences in humans, such as hyperthermia and neurocognitive deficits. Although MDMA consumption has been associated with visual problems, the effects of this recreational drug in retinal physiology have not been addressed hitherto. In this work, we evaluated the effect of a...

Modeling chronic brain exposure to amphetamines using primary rat neuronal cortical cultures.

Neuroscience September 26, 2014 T B Nogueira, Silvana Da Costa Araújo, F Carvalho et al.

Amphetamine-type psychostimulants (ATS) are used worldwide by millions of patients for several psychiatric disorders. Amphetamine (AMPH) and "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of chronic ATS exposure to neurons and brain aging is still undisclosed. Current neuronal culture paradigms are designed to access acute ATS toxicity. We report for...

DOI: 10.1016/j.neuroscience.2014.07.009 (opens in new tab) Full text (opens in new tab) Amphetamines Chronic exposure Cortical neurons Long-term neuronal cultures +2

MDMA impairs mitochondrial neuronal trafficking in a Tau- and Mitofusin2/Drp1-dependent manner.

Archives of Toxicology August 2014 Daniel José Barbosa, Roman Serrat, Serena Mirra et al.

Identification of the mechanisms by which drugs of abuse cause neuronal dysfunction is essential for understanding the biological bases of their acute and long-lasting effects in the brain. Here, we performed real-time functional experiments of axonal transport of mitochondria to explore the role of in situ mitochondrial dysfunction in 3,4-methylenedioxymethamphetamine (MDMA; "ecstasy")-related...

The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

Toxicological sciences : an official journal of the Society of Toxicology June 2014 Daniel José Barbosa, Roman Serrat, Serena Mirra et al.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and...

DOI: 10.1093/toxsci/kfu042 (opens in new tab) Full text (opens in new tab) 3,4-Methylenedioxymethamphetamine MDMA MDMA'S Metabolites Mitochondrial dysfunction Mitochondrial fusion/fission +2

"Ecstasy"-induced toxicity in SH-SY5Y differentiated cells: role of hyperthermia and metabolites.

Archives of Toxicology February 2014 Daniel José Barbosa, João Paulo Capela, Renata Silva et al.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a recreational hallucinogenic drug of abuse known to elicit neurotoxic properties. Hepatic formation of neurotoxic metabolites is thought to play a major role in MDMA-related neurotoxicity, though the mechanisms involved are still unclear. Here, we studied the neurotoxicity mechanisms and stability of MDMA and 6 of its major human...

Neurotoxicity of "ecstasy" and its metabolites in human dopaminergic differentiated SH-SY5Y cells.

Toxicology Letters February 4, 2013 Patrícia Silva Ferreira, Tiago Bernandes Nogueira, Vera Marisa Costa et al.

"Ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) is a widely abused recreational drug, reported to produce neurotoxic effects, both in laboratory animals and in humans. MDMA metabolites can be major contributors for MDMA neurotoxicity. This work studied the neurotoxicity of MDMA and its catechol metabolites, α-methyldopamine (α-MeDA) and N-methyl-α-methyldopamine (N-Me-α-MeDA) in human...

The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons.

Neurotoxicology January 2013 João Paulo Capela, Silvana Da Costa Araújo, Vera Marisa Costa et al.

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar...

Pro‐oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes

British Journal of Pharmacology April 21, 2011 Daniel José Barbosa, João Paulo Capela, Jorge M.A. Oliveira et al. 60 citations

BACKGROUND AND PURPOSE: 3,4-Methylenedioxymethamphetamine (MDMA or 'Ecstasy') is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5-HT by monoamine oxidase (MAO), as well as the hepatic biotransformation of MDMA into pro-oxidant reactive metabolites is thought...

Effect of 3,4-methylenedioxyamphetamine on dendritic spine dynamics in rat neocortical neurons--involvement of heat shock protein 27.

Brain Research January 25, 2011 Karsten Ruscher, Eduarda Fernandes, João Paulo Capela et al.

Along with chronic neurotoxic effects, the long-term consumption of amphetamines has been associated to psychiatric symptoms and memory disturbances. Dendritic spine dynamics have been discussed as a possible morphological correlate. However, the underlying mechanisms are still elusive. 3,4-Methylenedioxyamphetamine (MDA), a major drug of abuse and a main metabolite after...

Metabolic interactions between ethanol and MDMA in primary cultured rat hepatocytes.

Toxicology April 11, 2010 Helena Pontes, Paula Guedes de Pinho, Eduarda Fernandes et al.

3,4-Methylenedioxymethamphetamine (MDMA; ecstasy), a drug of abuse commonly consumed at rave parties, is often taken in a polydrug abuse scenario, ethanol being one of the most associated drugs. Both MDMA and ethanol are mainly metabolized in the liver with formation of toxic metabolites. Our working hypothesis is that ethanol can modify the metabolism of MDMA through the cytochrome P450...

Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type A.

Addiction Biology April 2009 Ema Alves, Teresa Summavielle, Cecília Juliana Alves et al.

The administration of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') to the rat results in mitochondrial oxidative damage in the central nervous system, namely lipid and protein oxidation and mitochondrial DNA deletions with subsequent impairment of the correspondent protein expression. Although these toxic effects were shown to be prevented by monoamine oxidase B...

Acetyl-L-carnitine provides effective in vivo neuroprotection over 3,4-methylenedioximethamphetamine-induced mitochondrial neurotoxicity in the adolescent rat brain.

Neuroscience January 23, 2009 E Alves, Z Binienda, F Carvalho et al.

3,4-Methylenedioximethamphetamine (MDMA, ecstasy) is a worldwide abused stimulant drug, with persistent neurotoxic effects and high prevalence among adolescents. The massive release of 5-HT from pre-synaptic storage vesicles induced by MDMA followed by monoamine oxidase B (MAO-B) metabolism, significantly increases oxidative stress at the mitochondrial level. l-Carnitine and its ester,...

Synergistic toxicity of ethanol and MDMA towards primary cultured rat hepatocytes.

Toxicology December 5, 2008 Helena Pontes, Carla Sousa, Renata Silva et al.

Ethanol is frequently consumed along with 3,4-methylenedioxymethamphetamine (MDMA; ecstasy). Since both compounds are hepatotoxic and are metabolized in the liver, an increased deleterious interaction resulting from the concomitant use of these two drugs seems plausible. Another important feature of MDMA-induced toxicity is hyperthermia, an effect known to be potentiated after continuous...

Neuropeptide Y protects retinal neural cells against cell death induced by ecstasy.

Neuroscience March 3, 2008 A R Alvaro, J Martins, A C Costa et al.

Ecstasy (3,4-methylenedioxymethamphetamine; MDMA) has potent CNS stimulant effects. Besides the acute effects of MDMA, such as psychomotor activation, euphoria, decreased appetite, and hyperthermia, long-term damage of dopaminergic and serotonergic nerve terminals in multiple brain areas have also been reported. Although some studies have demonstrated that considerable amounts of MDMA reach the...

Ecstasy induces apoptosis via 5-HT(2A)-receptor stimulation in cortical neurons.

Neurotoxicology July 2007 João Paulo Capela, Eduarda Fernandes, Fernando Remião et al.

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a psychoactive and hallucinogenic drug of abuse. MDMA has been shown to produce neurotoxicity both in animals and humans. MDMA and other amphetamines induce serotonergic and dopaminergic terminal neurotoxicity and also neurodegeneration in areas including the cortex, hippocampus, striatum and thalamus. Herein, we investigated the...

Neurotoxicity mechanisms of thioether ecstasy metabolites.

Neuroscience June 8, 2007 J P Capela, Carla Macedo, P S Branco et al.

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy"), is a widely abused, psychoactive recreational drug that is known to induce neurotoxic effects. Human and rat hepatic metabolism of MDMA involves N-demethylation to 3,4-methylenedioxyamphetamine (MDA), which is also a drug of abuse. MDMA and MDA are O-demethylenated to N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and alpha-methyldopamine...

Synthesis and Cyclic Voltammetry Studies of 3,4-Methylenedioxymethamphetamine (MDMA) Human Metabolites

JOURNAL OF HEALTH SCIENCE 2007 Carla Macedo, Paula S. Branco, Luı́sa M. Ferreira et al. 36 citations

3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a widely abused, psychoactive recreational drug. There are growing evidences that the MDMA neurotoxic profile may be highly dependent on its hepatic metabolism. MDMA metabolism leads to the production of highly reactive derivates, namely catechols, catechol thioethers, and quinones. In this study the electrochemical oxidation-reduction...

DOI: 10.1248/jhs.53.31 (opens in new tab) MDMA Ecstasy Cyclic voltammetry Catechol +3

Metabolic pathways of 4-bromo-2,5-dimethoxyphenethylamine (2C-B): analysis of phase I metabolism with hepatocytes of six species including human.

Toxicology January 5, 2005 Helena Carmo, Jan G Hengstler, Douwe De Boer et al. 85 citations

4-Bromo-2,5-dimethoxyphenethylamine (2C-B) is a psychoactive designer drug of abuse that is sold under the street names "Venus", "Bromo", "Erox", "XTC" or "Nexus". Concern has been raised because only little is known about its toxicity and metabolism in humans. In the present study we incubated 2C-B with human, monkey, dog, rabbit, rat and mouse hepatocytes to identify the metabolites formed...

DOI: 10.1016/j.tox.2004.07.004 (opens in new tab) Full text (opens in new tab) Drug metabolism Biotransformation Drug breakdown Drug processing +23

The toxicity of N-methyl-alpha-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine.

Toxicology August 5, 2004 Márcia Carvalho, Fernando Remião, Nuno Milhazes et al.

In the past decade, clinical evidence has increasingly shown that the liver is a target organ for 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") toxicity. The aims of the present in vitro study were: (1) to evaluate and compare the hepatotoxic effects of MDMA and one of its main metabolites, N-methyl-alpha-methyldopamine (N-Me-alpha-MeDA) and (2) to investigate the ability of antioxidants,...

Metabolism Is Required for the Expression of Ecstasy-Induced Cardiotoxicity in Vitro

Chemical Research in Toxicology April 27, 2004 Márcia Carvalho, Fernando Remião, Nuno Milhazes et al. 77 citations

Cardiovascular complications associated with 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse have increasingly been reported. The indirect effect of MDMA mediated by a sustained high level of circulating biogenic amines may contribute to the cardiotoxic effects, but other factors, like the direct toxic effects of MDMA and its metabolites in cardiac cells, remain to be investigated....

DOI: 10.1021/tx049960f (opens in new tab) MDMA Ecstasy Glutathione reductase Pharmacology +6

Hepatotoxicity of 3,4-methylenedioxyamphetamine and alpha-methyldopamine in isolated rat hepatocytes: formation of glutathione conjugates.

Archives of Toxicology January 2004 Márcia Carvalho, Nuno Milhazes, Fernando Remião et al.

The amphetamine designer drugs 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and its N-demethylated analogue 3,4-methylenedioxyamphetamine (MDA or "love") have been extensively used as recreational drugs of abuse. MDA itself is a main MDMA metabolite. MDMA abuse in humans has been associated with numerous reports of hepatocellular damage. Although MDMA undergoes extensive hepatic...