Identification of atmospheric pollutants control mechanisms during co-combustion of coal and non-toxic wastes

Doctoral dissertation for Ph.D. degree in Sustainable Chemistry

Development of chitosan-based microparticles for pulmonary drug delivery

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Evaluation of neuroprotective effects of natural extracts obtained from portuguese agro-food residues

Countries are currently faced with problems derived from changes in lifespan and an increase in lifestyle-related diseases. Neurodegenerative disorders such Parkinson’s (PD) and Alzheimer’s (AD) diseases are an increasing problem in aged societies. Data from World Alzheimer Report 2011 indicate that 36 million people worldwide are living with dementia. Oxidative stress has been associated with the development of AD and PD. Therefore there is interest to search for effective compounds or therapies to combat the oxidative damage in these diseases. Current evidence strongly supports a contribution of phenolic compounds present in fruits and vegetables to the prevention of neurodegenerative diseases such AD and PD. The industrial processing of a wide variety of fruits results in the accumulation of by-products without commercial value. Opuntia ficus-indica (cactus pear) is consumed fresh and processed like in juice. Prunnus avium (sweet cherry) is consumed fresh but the organoleptics characteristics of the fruits leads to the smaller and ragged fruits have no commercial value. Fruit extracts of both species has described to be rich in phenolic compounds and to have high antioxidant activities due to its composition. The aim of this work was assessing the efficacy of O. ficus-indica and P. avium by-products extracts obtained with conventional solvent extraction and pressurized liquid extraction in a neurodegeneration cell model. All extracts have protected neuroblastoma cells from H2O2-induced death at low, non-toxic levels, which approach to physiologically-relevant serum concentration. However, cherry extract has a slighter neuroprotective activity. The protective effect of Opuntia extracts are not conducted by a direct antioxidant activity since there are not decreases in intracellular ROS levels in cell treated with extracts and challenged with H2O2, while cherry extract neuroprotection seems to be due to a direct scavenging activity. Extracts from different biological matrixes seems to protect neuronal cells trough different cellular mechanisms.

Reactivity of human fetal and adult immortalized hepatocytes to potentially toxic bilirubin and bile acid species

Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Comparative effects of sediments contaminated by carcinogenic and non-carcinogenic PAHs in Dicentrarchus labrax: a semi-quantitative histopathological approach

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente

Overexpressing BDNF in Neural Stem Cells using non-viral gene delivery strategies

Dissertação para obtenção do Grau de Mestre em Biotecnologia

Toxicity of carcinogenic and non-carcinogenic Polycyclic Aromatic Hydrocarbons and their mixtures to aquatic organisms under ecologically-relevant scenarios

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous priority pollutants that tend to be trapped in aquatic sediments due to their high hydrophobicity. Nonetheless, the differential toxicological effects and mechanisms between the various classes of PAHs and their mixtures, as they invariably occur in the environment, are scarcely known, especially under ecologically-relevant scenarios. This thesis aimed at establishing a bridge between the study of mechanistic pathways and environmental monitoring of carcinogenic and non-carcinogenic PAHs, by introducing ecological-relevance in the research with model PAHs. A first bioassay conducted in situ with the mussel Mytilus edulis demonstrated that, dredging operations in harbours increase PAH bioavailability, eliciting genotoxicity, and showed that established environmental guidelines underestimate risk. Subsequent ex situ bioassays were performed with the carcinogenic benzo[b]fluoranthene (B[b]F) and non-carcinogenic phenantrene (Phe), selected following preceding results, and revealed that low-moderate concentrations of these PAHs in spiked sediments induce genotoxic effects to the clam Ruditapes decussatus, therefore contradicting the general notion that bivalves are less sensitive to PAHs than vertebrates due to inefficient bioactivation. Also, it was demonstrated that passive samplers permit inferring on PAH bioavailability but not on bioaccumulation or toxic effects. On the other hand, sea basses (Dicentrarchus labrax), yielded a complex pattern of effects and responses, relatively to genotoxicity, oxidative stress and production of specific metabolites, especially when exposed to mixtures of the PAHs which led to additive, if not synergistic, effects. It was shown that Phe may elicit significant genotoxicity especially in presence of B[b]F, even though the low, albeit realistic, exposure concentrations diluted dose- and time-independent relationships. The present work demonstrated that environmental quality guidelines underestimate the effects of PAHs in realistic scenarios and showed that the significant genotoxic and histopathological effects caused by mixed PAHs may not be reflected by oxidative stress- or CYP-related biomarkers. Besides important findings on the metabolism of PAH mixtures, the work calls for the need to re-evaluate the criteria for assessing risk and for the disclosure of more efficient indicators of toxicological hazard.