Browsing by Author "Fernandes, Eduarda"
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- Ecstasy-induced oxidative stress to adolescent rat brain mitochondria in vivo: influence of monoamine oxidase type APublication . Alves, Ema; Summavielle, Teresa; Alves, Cecília Juliana; Custódio, José Barata Antunes; Fernandes, Eduarda; Bastos, Maria de Lourdes; Tavares, Maria Amélia; Carvalho, FélixThe 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 inhibition, the role of monoamine oxidase A (MAO-A) in MDMA-mediated mitochondrial damage remains to be evaluated. Thus, the aim of the present study was to clarify the potential interference of a specific inhibition of MAO-A by clorgyline, on the deleterious effects produced by a binge administration of a neurotoxic dose of MDMA (10 mg MDMA/kg of body weight, intraperitoneally, every 2 hours in a total of four administrations) to an adolescent rat model. The parameters evaluated were mitochondrial lipid peroxidation, protein carbonylation and expression of the respiratory chain protein subunits II of reduced nicotinamide adenine dinucleotide dehydrogenase (NDII) and I of cytochrome oxidase (COXI). Considering that hyperthermia has been shown to contribute to the neurotoxic effects of MDMA, another objective of the present study was to evaluate the body temperature changes mediated by MDMA with a MAO-A selective inhibition by clorgyline. The obtained results demonstrated that the administration of a neurotoxic binge dose of MDMA to an adolescent rat model previously treated with the specific MAO-A inhibitor, clorgyline, resulted in synergistic effects on serotonin- (5-HT) mediated behaviour and body temperature, provoking high mortality. Inhibition of MAO-A by clorgyline administration had no protective effect on MDMA-induced alterations on brain mitochondria (increased lipid peroxidation, protein carbonylation and decrease in the expression of the respiratory chain subunits NDII and COXI), although it aggravated MDMA-induced decrease in the expression of COXI. These results reinforce the notion that the concomitant use of MAO-A inhibitors and MDMA is counter indicated because of the resulting severe synergic toxicity.
- Electrochemical sensing of ecstasy with electropolymerized molecularly imprinted poly(o-phenylenediamine) polymer on the surface of disposable screen-printed carbon electrodesPublication . Couto, Rosa A.S.; Costa, Séfora S.; Mounssef, Bassim; Pacheco, João; Fernandes, Eduarda; Carvalho, Félix; Rodrigues, Cecília M.P.; Delerue-Matos, Cristina; Braga, Ataualpa A.C.; Moreira Gonçalves, Luís; Quinaz, M. BeatrizThis study demonstrates the ability of an electrochemical sensor based on molecularly imprinted polymers (MIPs) to selectively quantify 3,4-methylenedioxymethamphetamine (MDMA), also known as ecstasy, in biological samples. The device was constructed using ortho-phenylenediamine (o-PD) as the MIP’s building monomer at the surface of a screen-printed carbon electrode (SPCE). The step-by-step construction of the SPCE-MIP sensor was characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Density functional theory (DFT) calculations and modelling were performed not only to understand template-monomer interaction but also to comprehend which possible polymer structure - linear or ramified poly(o-PD) – indeed interacts with the analyte. The prepared sensor worked by directly measuring the MDMA oxidation signal through square-wave voltammetry (SWV) after an incubation period of 10 min. Several parameters were optimized, such as the monomer/template ratio, the number of electropolymerization scanning cycles, and the incubation period, to obtain the best sensing efficiency. Optimized sensors exhibited suitable selectivity, repeatability (2.6%), reproducibility (7.7%) and up to one month of stable response. A linear range up to 0.2 mmol L−1 was found with an r2 of 0.9990 and a limit of detection (LOD) and quantification (LOQ) of 0.79 and 2.6 μmol L−1 (0.15 and 0.51 μg mL−1), respectively. The proposed sensor was successfully applied to human blood serum and urine samples, showing its potential for application in medicine and in forensic sciences.
- Pyrazoles as potential modulators of inflammation through the inhibition of COX2 activity and human leukocytes' oxidative burstPublication . Silva, Jorge; Rocha, Sónia; Silva, Vera L. M.; Silva, Artur M. S.; Moreira, Fernando; Fernandes, Eduarda; Freitas, MarisaThe inflammatory process is a complex and tightly regulated cascade of events that involves the production of prostaglandins (PG) by the inducible isoform cyclooxygenase 2 (COX-2) and the production of reactive pro-oxidant species. When the production of these mediators becomes excessive, it can lead to chronic inflammation and associated diseases such as diabetes, rheumatoid arthritis, and cancer. Unfortunately, many existing anti-inflammatory agents are associated with unwanted side effects. Therefore, there is a critical need to discover new and effective compounds that can modulate the inflammatory cascade. In this study, an extensive panel of structurally related pyrazoles holding diverse structures and substitutions were tested in vitro against human COX-2, and ex vivo in human whole blood, through the measurement of prostaglandin E2 (PGE2) production. Their potential inhibitory effect against human leukocytes’ oxidative burst was also studied. The results showed that some of the tested compounds had a significant inhibitory effect on COX2 activity, and pyrazoles 4 and 11 (Figure 1) excelled as the most potent inhibitors, with IC50 < 25 µM. Nonetheless, among the tested compounds only 1 was able to inhibit both the COX-2 activity and the PGE2 production. The tested pyrazoles, namely pyrazole 4, also demonstrated a potential inhibitory effect (IC50 < 5 µM) against human leukocytes’ oxidative burst. These results represent a significant contribution for the design and development of new anti-inflammatory molecules.