Multifunctional biomolecular systems for new methods of decontamination, protection and toxicological assessment

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Publications

BSA-PEG Hydrogel: A Novel Protein-Ligand Binding 3D Matrix

Publication . Coelho, Carlos D. F.; Jesus, João A.; Vaz, Daniela C.; Lagoa, Ricardo; Moreno, Maria João

Hydrogel materials have good biomimetic properties and high potential for biomedical and bioanalytical applications. In this work, a hydrogel of serum albumin crosslinked with poly-(ethylene glycol) was prepared and characterized for its water content, protein structure and stability. The ability of the hydrogel to bind small molecule ligands with different hydrophobicity was evaluated using a homologous series of amphiphiles (NBD-Cn, n = 4, 6 and 8) and the calculated binding affinities were similar to that of free protein in solution. Overall, the results indicate this type of hydrogel system as a convenient tool for studying the binding of xenobiotics to tissue proteins.

2022-08-25Journal article

Open access

Reassessment of the experimental skin permeability coefficients of polycyclic aromatic hydrocarbons and organophosphorus pesticides

Publication . Silva, João; Marques da Silva, Dorinda; Lagoa, Ricardo

2021-05-09Journal article

Open access

Molecular mechanisms linking environmental toxicants to cancer development: Significance for protective interventions with polyphenols

Publication . Lagoa, Ricardo; Marques-da-Silva, Dorinda; Diniz, Mário; Daglia, Maria; Bishayee, Anupam

Human 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.

2022-11Journal article

Open access

Anthocyanins, effects in mitochondria and metabolism

Publication . Marques-da-Silva, Dorinda; Rodrigues, Joaquim Rui; Lagoa, Ricardo

Alterations 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.

2021Book part

Restricted access

Humic acid aggregates with laccase and decreases the performance of the enzyme catalytic systems through various mechanisms

Publication . Lopes, João; Marques-da-Silva, Dorinda; Peralta, Cláudia; Rodrigues, Joaquim Rui; Vaz, Daniela; Lagoa, Ricardo

Laccases are among the best-rated enzymes for industrial and environmental applications, yet their use in bioremediation is limited by interference from environmental components like humic acid (HA). This study evaluated HA impact on the oxidation of 2,2 ′-azino-bis-(3-ethylbenzothiazoline-6-sulphonate (ABTS) and two model pollutants — anthracene and methyl orange — by laccase( mediator) systems. HA consistently diminished conversion rates, with EC50 values between 5 and 51 mg/L suggesting diverse inhibitory mechanisms. We investigated potential mechanisms including substrate sequestration, radical quenching, and chelation of laccase coppers by HA. Incubations with free and immobilized HA showed that adsorption can impede anthracene degradation, at least at high concentrations, but not methyl orange. Using chemically generated ABTS radical and azide-blocked enzyme, it was demonstrated that HA scavenges free radicals produced by laccase, though this alone did not fully explain the observed interference with catalysis. Further assays with metal chelator and added copper or calcium ruled out HA binding to the laccase metal centers. Instead, data from molecular docking, f luorescence, light scattering, and microscopy revealed that HA forms micrometer-scale aggregates with laccase that encapsulate the enzyme. This newly identified mechanism likely applies broadly to laccase-based systems and must be considered in applications involving aqueous media containing humic substances.

2025-09Journal article

Open access