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- Registered human trials addressing environmental and occupational toxicant exposures: Scoping review of immunological markers and protective strategiesPublication . Marques da Silva, Dorinda; Videira, Paula Alexandra; Lagoa, RicardoExposure to pollution is a worldwide societal challenge participating in the etiology and progression of different diseases. However, the scarce information hinders our understanding of the actual level of human exposure and its specific effects. Inadequate and excessive immune responses underlie diverse chronic diseases. Yet, it is unclear which and how toxicant exposures affect the immune system functions. There is a multiplicity of immunological outcomes and biomarkers being studied in human trials related to exposure to different toxicants but still without clear evidence of their value as biomarkers of exposure or effect. The main aim of this study was to collect scientific evidence and identify relevant immunological biomarkers used at the clinical level for toxicant exposures. We used the platform clinical trials.gov as a database tool. First, we performed a search combining research items related to toxicants and immunological parameters. The resulting117 clinical trials were examined for immune-related outcomes and specific biomarkers evaluated in subjects exposed to occupational and environmental toxicants. After categorization, relevant immunological outcomes and biomarkers were identified related to systemic and airway inflammation, modulation of immune cells, allergy and autoimmunity. In general, the immune markers related to inflammation are more frequently investigated for exposure to pollutants, namely IL-6, C-reactive protein (CRP) and nitric oxide (NO). Nevertheless, the data also indicated that prospective biomarkers of effect are gaining ground and a guiding representation of the established and novel biomarkers is suggested for upcoming trials. Finally, potential protective strategies to mitigate the adverse effects of specific toxicants are underlined for future studies.
- Anthocyanins, effects in mitochondria and metabolismPublication . Marques-da-Silva, Dorinda; Rodrigues, Joaquim Rui; Lagoa, RicardoAlterations in mitochondrial function, cellular redox signaling, and metabolism participate in the etiology and progression of different pathological conditions, such as diabetes, cancer, cardiovascular, and neurodegenerative diseases. Epidemiological, preclinical, and clinical studies indicate that anthocyanins afford therapeutic benefits for these pathologies. It is thus important to revise the effects of anthocyanins on mitochondria and metabolism that hold potential for the development of novel health protective methods. The studies available support the ability of certain anthocyanins to prevent damage to mitochondria and to sustain its function. Evidence is more compelling for cyanidin and delphinidin compounds, but promising data could also be found for malvidin, pelargonidin, and protocatechuic acid. Additionally, berry extracts also demonstrated positive outcomes in different models of neurodegeneration, endothelial dysfunction, myocardial damage, metabolic disorders, longevity, and cancer. At the molecular level, major anthocyanins can modulate the expression and activity of mitochondrial proteins, apoptotic and biogenesis factors, antioxidant defenses, inflammation, and the AMPK pathway. Noteworthy, anthocyanins could balance abnormalities in ROS production, respiration, and mitochondrial fragmentation in cells exposed to toxicants or oxidizing agents.
- Towards the Development of Delivery Systems of Bioactive Compounds With Eyes Set on PharmacokineticsPublication . Silva, João S.; Marques-da-Silva, Dorinda; Lagoa, RicardoDelivery systems carrying natural bioactive compounds for enhanced targeting and controlled release are capturing increasing attention. High loadings and sustained release are common design goals. However, in the case of compounds naturally present in human nutrition and physiology, further efforts are justified to optimize their bioactivity and promote clinical success. In this work, it is proposed a specific attention to the regulation of drug temporal presentation as important factor to obtain novel multifunctional delivery systems meeting higher therapeutic efficiencies. Case studies on the relation between drug release dynamics and biological responses are presented for some major delivery strategies and different bioactive molecules. Pharmacokinetic essential concepts and issues concerning the multi-target mode of action typical of the pharmacological properties of natural compounds are discussed in the perspective of improving the development of efficient drug formulations. Several classes of controlled release systems are considered through the chapter, and laboratory setups for testing films and particulate delivery systems are detailed, as well as the application of models for kinetic analysis. Descriptions are illustrated with experimental results obtained with caffeine and epicatechin in our laboratory. Future investigations will benefit from preclinical and clinical evaluation of the new formulations developed by emerging approaches and tools that are being suggested by diverse authors.
- Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenolsPublication . Lagoa, Ricardo; Marques-da-Silva, Dorinda; Diniz, Mário; Daglia, Maria; Bishayee, AnupamHuman exposure to environmental toxicants with diverse mechanisms of action is a growing concern. In addition to well-recognized carcinogens, various chemicals in environmental and occupational settings have been sug-gested to impact health, increasing susceptibility to cancer by inducing genetic and epigenetic changes. Accordingly, in this review, we have discussed recent insights into the pathological mechanisms of these chemicals, namely their effects on cell redox and calcium homeostasis, mitochondria and inflammatory signaling, with a focus on the possible implications for multi-stage carcinogenesis and its reversal by poly- phenols. Plant-derived polyphenols, such as epigallocatechin-gallate, resveratrol, curcumin and anthocyanins reduce the incidence of cancer and can be useful nutraceuticals for alleviating the detrimental outcomes of harmful pollutants. However, development of therapies based on polyphenol administration requires further studies to validate the biological efficacy, identifying effective doses, mode of action and new delivery forms. Innovative microphysiological testing models are presented and specific proposals for future trials are given. Merging the current knowledge of multifactorial actions of specific polyphenols and chief environmental toxi- cants, this work aims to potentiate the delivery of phytochemical-based protective treatments to individuals at high-risk due to environmental exposure.
- Reassessment of the experimental skin permeability coefficients of polycyclic aromatic hydrocarbons and organophosphorus pesticidesPublication . Silva, João; Marques da Silva, Dorinda; Lagoa, Ricardo