Browsing by Author "Bastos, Maria de Lourdes"
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- 2-Styrylchromones as novel inhibitors of xanthine oxidase. A structure-activity studyPublication . Fernandes, Eduarda; Carvalho, Félix; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Bastos, Maria de LourdesThe purpose of this study was the evaluation of the xanthine oxidase (XO) inhibition produced by some synthetic 2-styrylchromones. Ten polyhydroxylated derivatives with several substitution patterns were synthesised, and these and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid from xanthine. The synthesised 2-styrylchromones inhibited xanthine oxidase in a concentration-dependent and non-competitive manner. Some IC50 values found were as low as 0.55mM, which, by comparison with the IC50 found for allopurinol (5.43 mM), indicates promising new inhibitors. Those 2-styrylchromones found to be potent XO inhibitors should be further evaluated as potential agents for the treatment of pathologies related to the enzyme’s activity, as is the case of gout, ischaemia/ reperfusion damage, hypertension, hepatitis and cancer.
- Amanita phalloides poisoning: Mechanisms of toxicity and treatmentPublication . Garcia, Juliana; Costa, Vera M.; Carvalho, Alexandra T.P.; Baptista, Paula; Pinho, P. Guedes de; Bastos, Maria de Lourdes; Carvalho, FélixAmanita phalloides, also known as 'death cap', is one of the most poisonous mushrooms, being involved in the majority of human fatal cases of mushroom poisoning worldwide. This species contains three main groups of toxins: amatoxins, phallotoxins, and virotoxins. From these, amatoxins, especially α-amanitin, are the main responsible for the toxic effects in humans. It is recognized that α-amanitin inhibits RNA polymerase II, causing protein deficit and ultimately cell death, although other mechanisms are thought to be involved. The liver is the main target organ of toxicity, but other organs are also affected, especially the kidneys. Intoxication symptoms usually appear after a latent period and may include gastrointestinal disorders followed by jaundice, seizures, and coma, culminating in death. Therapy consists in supportive measures, gastric decontamination, drug therapy and, ultimately, liver transplantation if clinical condition worsens. The discovery of an effective antidote is still a major unsolved issue. The present paper examines the clinical toxicology of A. phalloides, providing the currently available information on the mechanisms of toxicityinvolved and on the current knowledge on the treatment prescribed against this type of mushrooms. Antidotal perspectives will be raised as to set the pace to new and improved therapy against these mushrooms.
- Antioxidant activity and phenolic contents of Olea europaea L. leaves sprayed with different cooper formulationsPublication . Ferreira, Isabel C.F.R.; Barros, Lillian; Soares, Maria Elisa; Bastos, Maria de Lourdes; Pereira, J.A.The presence of cooper can catalyse oxidation of fatty acid chains, exerting a deleterious influence over shelf life. Transition metals, which possess two or more valence states with a sui tab le redox potential, act as pro-oxidants even at concentrations lower than 0.1 ppm, and could affect the speed of autoxidation and the direction of hydroperoxide breakdown to volatile le compounds. Being copper a transition metal that even, in small concentration, is a very potent oxidation catalyst, can enter a redox reaction, giving rise to consequent lipid peroxidation phenomenon due to the free radicals producing.
- Antioxidant activity and phenolic contents of Olea europaea L. leaves sprayed with different copper formulationsPublication . Ferreira, Isabel C.F.R.; Barros, Lillian; Soares, Maria Elisa; Bastos, Maria de Lourdes; Pereira, J.A.Olive trees (Olea europaea L. Cv. Cobranc¸osa) from the northeast of Portugal were sprayed with three different copper formulations [bordeaux mixture (copper sulphate + calcium hydroxide - 20% Cu), copper hydroxide (40% Cu) and copper oxychloride (50% Cu)] to control olive fungal diseases. The residues of copper in olive leaves, harvested at different times, were evaluated by atomic absorption spectrometry. At all the collection times, treated olive leaves had significantly higher copper contents, compared to the control. The different copper amounts in pesticide formulations lowered the leaves contents in total phenols and hence their antioxidant properties. Olive leaves sprayed with copper oxychloride possessed the highest copper levels and the lowest content in phenols, which influenced its antioxidant activity (higher EC50 values for reducing power, scavenging effect on DPPH radicals and inhibition of erythrocyte hemolysis). Leaves without copper residues proved to be a good natural source of antioxidants, giving values comparable to the reference compounds.
- A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin BPublication . Garcia, Juliana; Costa, Vera M.; Carvalho, Alexandra T.P.; Silvestre, Ricardo; Duarte, José A.; Dourado, Daniel F.A.R.; Arbo, Marcelo D.; Baltazar, Teresa; Dinis-Oliveira, Ricardo Jorge; Baptista, Paula; Bastos, Maria de Lourdes; Carvalho, FélixAmanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. α-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to α-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of α-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by α-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal α-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to α-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-α-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with α-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in α-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.
- Co-ingestion of amatoxins and isoxazoles-containing mushrooms and successful treatment: A case reportPublication . Garcia, Juliana; Costa, Vera M.; Costa, Ana Elisa; Andrade, Sérgio; Carneiro, Ana Cristina; Conceição, Filipe; Paiva, José Artur; Pinho, P. Guedes de; Baptista, Paula; Bastos, Maria de Lourdes; Carvalho, FélixMushroom poisonings occur when ingestion of wild mushrooms containing toxins takes place, placing the consumers at life-threatening risk. In the present case report, an unusual multiple poisoning with isoxazoles- and amatoxins-containing mushrooms in a context of altered mental state and poorly controlled hypertension is presented. A 68-year-old female was presented to São João hospital (Portugal) with complaints of extreme dizziness, hallucinations, vertigo and imbalance, 3 h after consuming a stew of wild mushrooms. The first observations revealed altered mental state and elevated blood pressure. The examination of cooked mushroom fragments allowed a preliminary identification of Amanita pantherina. Gas chromatography-mass spectrometry (GC-MS) showed the presence of muscimol in urine. Moreover, through high-performance liquid chromatography-ultraviolet detection (HPLC-UV) analysis of the gastric juice, the presence of α-amanitin was found, showing that amatoxins-containing mushrooms were also included in the stew. After 4 days of supportive treatment, activated charcoal, silybin and N-acetylcysteine, the patient recovered being discharged 10 days post-ingestion with no organ complications. The prompt and appropriate therapy protocol for life-threatening amatoxins toxicity probably saved the patient's life as oral absorption was decreased and also supportive care was immediately started.
- Copper and lead residues in olives after olive tree treatments with three different copper formulations.Publication . Soares, Maria Elisa; Pereira, J.A.; Bastos, Maria de Lourdes
- Copper residues in olives after olive tree treatments with three different copper formulations.Publication . Soares, Maria Elisa; Pereira, J.A.; Bastos, Maria de Lourdes
- Determination of amatoxins and phallotoxins in Amanita phalloides mushrooms from northeastern Portugal by HPLC-DAD-MSPublication . Garcia, Juliana; Oliveira, Ana Paula Leandro; Pinho, P. Guedes de; Freitas, Victor; Carvalho, Alexandra T.P.; Baptista, Paula; Pereira, Eric Carvalho; Bastos, Maria de Lourdes; Carvalho, FélixAmanita phalloides is a toxic mushroom responsible for the majority of deaths occurring after mushrooms ingestion, mainly due to amatoxins. In the present study the contents and distribution of the major amatoxins and phallotoxins in different tissues of A. phalloides from two different sites of Portugal were analyzed by liquid chromatography (LC) coupled to diode array (DAD) and mass spectrometry (MS) detection. The main toxins were separated by LC and its chemical structures confirmed by MS. a-Amanitin contents in caps, stipe and volva tissues were quantified by RP-HPLC. The results show that caps have the highest content of amatoxins, whereas the volva was richest in phallotoxins. Moreover variability in the toxins composition from different geographic sites was also observed. This study provides for the first time the content of toxins in A. phalloides from Portugal.
- Hepatoprotective activity of 2-styrylchromone derivatives against the pro-oxidant hepatotoxic effect elicited by tert-butylhydroperoxide in freshy isolated rat hepatocytesPublication . Fernandes, Eduarda; Carvalho, Márcia; Carvalho, Félix; Silva, Artur; Santos, Clementina M.M.; Pinto, Diana; Cavaleiro, José; Bastos, Maria de Lourdes
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