Percorrer por autor "de Lourdes Bastos, Maria"
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- 3,4-Methylenedioxymethamphetamine hepatotoxicity under the heat stress condition: novel insights from in vitro metabolomic studiesPublication . Araújo, Ana Margarida; Enea, Maria; Fernandes, Eduarda; Carvalho, Félix; de Lourdes Bastos, Maria; Carvalho, Márcia; Guedes de Pinho, PaulaHyperthermia has been extensively reported as a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. In this work, we used a sensitive untargeted metabolomic approach based on gas chromatography-mass spectrometry to evaluate the impact of hyperthermia on the hepatic metabolic changes caused by MDMA. For this purpose, primary mouse hepatocytes were exposed to subtoxic (LC01 and LC10) and toxic (LC30) concentrations of MDMA for 24 h, at 37 or 40.5 °C (simulating body temperature increase after MDMA consumption), and alterations on both intracellular metabolome and extracellular volatilome were evaluated. Multivariate analysis showed that metabolic patterns clearly discriminate MDMA treated cells from control cells, both in normothermic and hyperthermic conditions. The metabolic signature was found to be largely common to MDMA subtoxic and toxic concentrations, although with evident differences in the magnitude of response, with metabolic changes significantly more pronounced at 40.5 °C. Discriminant metabolites associated with MDMA-induced hepatotoxicity are mostly involved in the amino acid metabolism, aminoacyl tRNA biosynthesis, glutathione metabolism, tricarboxylic acid cycle, and pyruvate metabolism. Moreover, our metabolomic findings were corroborated by classical toxicity parameters, demonstrating the high sensitivity of this omic approach to assess molecular-level effects. Overall, this study indicates that MDMA triggers significant metabolic alterations on hepatic cells, even at low concentrations, that are clearly exacerbated at high temperatures. These findings provide new metabolic pieces to solve the puzzle of MDMA's hepatotoxicity mechanism and emphasize the increased risks of MDMA abuse due to the thermogenic action of the drug.
- Effect of subtoxic and toxic concentrations of galactosamine in the metabolome of primary mouse hepatocytesPublication . Araújo, Ana Margarida; Lima, Ana Rita; de Lourdes Bastos, Maria; Carvalho, Félix; Carvalho, Márcia; de Pinho, Paula Guedes
- Khat and synthetic cathinones: a reviewPublication . Valente, Maria João; Guedes de Pinho, Paula; de Lourdes Bastos, Maria; Carvalho, Félix; Carvalho, MárciaFor centuries, 'khat sessions' have played a key role in the social and cultural traditions among several communities around Saudi Arabia and most East African countries. The identification of cathinone as the main psychoactive compound of khat leaves, exhibiting amphetamine-like pharmacological properties, resulted in the synthesis of several derivatives structurally similar to this so-called natural amphetamine. Synthetic cathinones were primarily developed for therapeutic purposes, but promptly started being misused and extensively abused for their euphoric effects. In the mid-2000's, synthetic cathinones emerged in the recreational drug markets as legal alternatives ('legal highs') to amphetamine, 'ecstasy', or cocaine. Currently, they are sold as 'bath salts' or 'plant food', under ambiguous labels lacking information about their true contents. Cathinone derivatives are conveniently available online or at 'smartshops' and are much more affordable than the traditional illicit drugs. Despite the scarcity of scientific data on these 'legal highs', synthetic cathinones use became an increasingly popular practice worldwide. Additionally, criminalization of these derivatives is often useless since for each specific substance that gets legally controlled, one or more structurally modified analogs are introduced into the legal market. Chemically, these substances are structurally related to amphetamine. For this reason, cathinone derivatives share with this drug both central nervous system stimulating and sympathomimetic features. Reports of intoxication and deaths related to the use of 'bath salts' have been frequently described over the last years, and several attempts to apply a legislative control on synthetic cathinones have been made. However, further research on their pharmacological and toxicological properties is fully required in order to access the actual potential harm of synthetic cathinones to general public health. The present work provides a review on khat and synthetic cathinones, concerning their historical background, prevalence, patterns of use, legal status, chemistry, pharmacokinetics, pharmacodynamics, and their physiological and toxicological effects on animals and humans.
- Role of autophagy, apoptosis and oxidative stress in the toxicity of β-keto amphetamines to human dopaminergic SH-SY5Y cellsPublication . Valente, Maria João; Amaral, Cristina; Correia-da-Silva, Georgina; Duarte, José Alberto; de Lourdes Bastos, Maria; Carvalho, Félix; de Pinho, Paula Guedes; Carvalho, Márcia