Browsing by Author "Carvalho, F."
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- Contribution of catecholamine reactive intermediates and oxidative stress to the pathologic features of heart diseasesPublication . Costa, V.M.; Carvalho, F.; L. Bastos, M.; A. Carvalho, R.; Carvalho, Márcia; Remiao, F.Pathologic heart conditions, particularly heart failure (HF) and ischemia-reperfusion (I/R) injury, are characterized by sustained elevation of plasma and interstitial catecholamine levels, as well as by the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Despite the continuous and extensive research on catecholamines since the early years of the XX(th) century, the mechanisms underlying catecholamine-induced cardiotoxicity are still not fully elucidated. The role of catecholamines in HF, stress cardiomyopathy, I/R injury, ageing, stress, and pheochromocytoma will be thoroughly discussed. Furthermore and although the noxious effects resulting from catecholamine excess have traditionally been linked to adrenoceptors, in fact, several evidences indicate that oxidative stress and the oxidation of catecholamines can have important roles in catecholamine-induced cardiotoxicity. Accordingly, the reactive intermediates formed during catecholamine oxidation have been associated with cardiac toxicity, both in in vitro and in vivo studies. An insight into the influence of ROS, RNS, and catecholamine oxidation products on several heart diseases and their clinical course will be provided. In addition, the source and type of oxidant species formed in some heart pathologies will be referred. In this review a special focus will be given to the research of cardiac pathologies where catecholamines and oxidative stress are involved. An integrated vision of these matters is required and will be provided along this review, namely how the concomitant surge of catecholamines and ROS occurs and how they can be interconnected. The concomitant presence of these factors can elicit peculiar and not fully characterized responses on the heart. We will approach the existing data with new perspectives as they can help explaining several controversial results regarding cardiovascular diseases and the redox ability of catecholamines.
- Contribution of oxidative metabolism to cocaine-induced liver and kidney damagePublication . Valente, M.J.; Carvalho, F.; Bastos, M.d.L.; de Pinho, P.G.; Carvalho, MárciaCocaine is a potent psychoactive illicit substance and its abuse represents a major health burden worldwide. The pharmacodynamics and toxicity of cocaine have been extensively documented, and are generally associated to its affinity towards neurotransmitters transporters and several receptors. However, drug-related formation of reactive compounds, as is the case of pro-oxidant reactive species, and interaction at molecular level is still an understudied matter. The involvement of oxidative stress (OS) in cocaine-induced toxicity has been reported in both human and animal models, in several organs and systems, including heart, liver, kidney, and central nervous system (CNS). Cytochrome P450 (CYP450)-mediated cocaine metabolism yields the reactive pro-oxidant compound norcocaine (NCOC) and further oxidative metabolites. Special emphasis should be given to the stable radical norcocaine nitroxide (NCOC-NO·), which plays a key role in cocaine-induced hepatotoxicity, either by entering a futile redox cycle with an N-oxidative metabolite, or by being further oxidized to a highly reactive ion. In fact, cocaine-induced generation of reactive oxygen species (ROS) and consequent OS has been postulated based on the reactivity of cocaine N-oxidative metabolites. Depletion of cellular antioxidant defenses and impairment of mitochondrial respiration have also been considered important causes of ROS production, and subsequent cell death mediated by cocaine. The present review provides a thorough description of the current knowledge on cocaine oxidative metabolism and its role on drug-induced liver and kidney damage.
- Metabolomic analysis of the toxicity pathways elicited by subtoxic concentrations of methylone in primary mouse hepatocytesPublication . Araújo, A.M.; Bastos, M.D.L.; Carvalho, F.; Carvalho, Márcia; Guedes de Pinho, Paula
- Simultaneous determination of amphetamine derivatives in human urine after SPE extraction and HPLC-UV analysisPublication . Soares, M. E.; Carvalho, Márcia; Carmo, H.; Remião, F.; Carvalho, F.; Bastos, M. L.Amphetamine derivatives are a class of compounds increasingly abused as recreational drugs in various regions of the world. Although d-amphetamine (AMPH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are among the most commonly used, the abuse of other designer drugs such as 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and 4-methylthioamphetamine (4-MTA) and their involvement in acute intoxications has been increasingly reported. There is evidence that abusers ingest these compounds either alone or in combination and the respective monitoring is important for both legal and health care purposes in hospital emergency. In the present study a simple and clean solid-phase extraction procedure from urine of AMPH and MDMA, and their major metabolites p-hydroxyamphetamine (OH-AMPH) and methylenedioxyamphetamine (MDA) and 2C-B and 4-MTA was developed. Analysis was performed by HPLC-UV and the precision of the technique was between 2.9 and 5.3% for all compounds. For the overall procedure, the precision values were between 3.3 and 5.9%. Recoveries obtained from spiked urines at three concentration levels were better than 84 +/- 4% for the six compounds. The limit of detection of the method for the compounds (between 5.3 and 84.0 ng) enables their identification in urine after ingestion of fatal and non-fatal doses. The main advantages of the present method lie in its simple, clean and reliable SPE extraction method of the six amphetamine derivatives from urine followed by their simultaneous detection and quantification by liquid chromatography with UV detection.
- βk-amphetamines: neurotoxicity triggered by methylone and MDPV in undifferentiated and differentiated SH-SY5Y cells and comparison to MDMAPublication . Valente, M.; Bastos, M.; Carvalho, F.; Guedes de Pinho, Paula; Carvalho, Márcia