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Med. Sci. Forum, 2022, BiTaP 2022

Biosystems in Toxicology and Pharmacology—Current Challenges

Online | 8–9 September 2022

Volume Editors: 
Ricardo Lagoa, ESTG-Polytechnic Institute of Leiria, Portugal
Paula Videira, FCT-NOVA University of Lisboa, Portugal
Manuel Aureliano, FCT-University of Algarve, Portugal

Number of Papers: 11
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Cover Story (view full-size image): Biological systems and models provide essential platforms for the evaluation of drugs and toxicants. From biomolecular systems comprising enzymes or antibodies, to a panoply of existing cell culture [...] Read more.
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4 pages, 445 KiB  
Proceeding Paper
BSA-PEG Hydrogel: A Novel Protein-Ligand Binding 3D Matrix
Med. Sci. Forum 2022, 11(1), 1; https://doi.org/10.3390/BiTaP-12878 - 25 Aug 2022
Viewed by 1153
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 763 KiB  
Proceeding Paper
The Growth Curve Method to Rapidly Derive the Antibacterial Potential of Polyoxovanadates
Med. Sci. Forum 2022, 11(1), 2; https://doi.org/10.3390/BiTaP-12790 - 10 Jul 2022
Viewed by 1003
Abstract
In previous studies (Marques-da-Silva et al., 2019), we measured the minimum inhibitory concentrations (MICs) of three polyoxovanadates, namely V10, MnV11, and MnV13, against Escherichia coli. MICs were obtained following the standard method, which requires a 16–20 h culture and might neglect the [...] Read more.
In previous studies (Marques-da-Silva et al., 2019), we measured the minimum inhibitory concentrations (MICs) of three polyoxovanadates, namely V10, MnV11, and MnV13, against Escherichia coli. MICs were obtained following the standard method, which requires a 16–20 h culture and might neglect the effects of the compounds’ metabolism during incubation. In this work, we studied the action of those compounds against Enterococcus faecalis by monitoring the bacterial growth kinetics, and we observed that the inhibition was evident from the beginning of the exponential phase. Notably, data collected from just a 7 h culture was enough to identify the compounds with stronger antibacterial activity according to standard MICs. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 636 KiB  
Proceeding Paper
Synthetic Membranes as an Alternative to Animal Skin to Investigate Dermal Permeation of Chlorpyrifos
Med. Sci. Forum 2022, 11(1), 3; https://doi.org/10.3390/BiTaP-12786 - 04 Jul 2022
Viewed by 751
Abstract
Chlorpyrifos is a pesticide revised as dangerous for human health. While dermal permeation of chlorpyrifos is still poorly investigated, alternatives to animal and/or human skin are demanded. In this work, the suitability of synthetic membranes as alternative models to study dermal permeation of [...] Read more.
Chlorpyrifos is a pesticide revised as dangerous for human health. While dermal permeation of chlorpyrifos is still poorly investigated, alternatives to animal and/or human skin are demanded. In this work, the suitability of synthetic membranes as alternative models to study dermal permeation of chlorpyrifos was investigated. Silicone and STRAT-M® membranes were tested on Franz cells using different receptor compositions. By adapting the concentration of ethanol in the receptor fluid, the results of chlorpyrifos permeation through both membranes were close to those found in human skin studies, supporting the use of those membranes as non-animal skin-equivalent models. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 819 KiB  
Proceeding Paper
Promotion of Dermal Permeation of Bioactive Compounds Using a Microneedle Device
Med. Sci. Forum 2022, 11(1), 4; https://doi.org/10.3390/BiTaP-12840 - 21 Jul 2022
Cited by 1 | Viewed by 837
Abstract
Several natural bioactive compounds are described for their beneficial effects to skin. Nevertheless, for some compounds, dermal absorption is a challenge, demanding new methods to enhance skin penetration. In this work, pre-treatment with a microneedle device was tested to promote the permeation of [...] Read more.
Several natural bioactive compounds are described for their beneficial effects to skin. Nevertheless, for some compounds, dermal absorption is a challenge, demanding new methods to enhance skin penetration. In this work, pre-treatment with a microneedle device was tested to promote the permeation of caffeine and epicatechin through ex vivo pig skin. The results indicated that the microneedle pre-treatment increased the permeation of both compounds at a similar range. Compared to untreated skin, more than 20% higher amounts of caffeine and epicatechin crossed the treated skin. The data support the application of microneedle systems to promote the dermal delivery of bioactive compounds. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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9 pages, 1097 KiB  
Proceeding Paper
The Cytotoxicity of Phorbol 12- Myristate 13-Acetate and Lipopolysaccharide on THP-1 Cells and an Optimized Differentiation Protocol
Med. Sci. Forum 2022, 11(1), 5; https://doi.org/10.3390/BiTaP-12785 - 02 Jul 2022
Cited by 1 | Viewed by 3347
Abstract
In order to evaluate the immunomodulatory potential of novel monofloral Irish honeys, THP-1 monocyte-derived macrophages provided a suitable cell-based model. THP-1 cells can be differentiated to macrophages using phorbol-12-myristate-13-acetate (PMA). Differentiated cells are then challenged with lipopolysaccharide (LPS) to stimulate the inflammatory cascade. [...] Read more.
In order to evaluate the immunomodulatory potential of novel monofloral Irish honeys, THP-1 monocyte-derived macrophages provided a suitable cell-based model. THP-1 cells can be differentiated to macrophages using phorbol-12-myristate-13-acetate (PMA). Differentiated cells are then challenged with lipopolysaccharide (LPS) to stimulate the inflammatory cascade. Few studies on the cytotoxic concentrations of these two compounds on THP-1 cells have been published. Therefore, the viability of treated THP-1 cells was initially evaluated using Trypan Blue dye exclusion (for PMA), the resazurin assay (for LPS), and propidium iodide (PI) staining (for both). The literature suggests that concentrations ranging from 100 ng/mL down to 5 ng/mL PMA are sufficient for THP-1 differentiation. Consequently, further elucidation of the differentiation potential of this sub-cytotoxic PMA concentration range was also evaluated using flow cytometric detection of the macrophage-specific CD14 cell surface marker. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 1214 KiB  
Proceeding Paper
Use of Lipid Vesicles for Revealing the Potential Contribution of Cytochrome C in the Metabolism of Environmental Toxicants
Med. Sci. Forum 2022, 11(1), 6; https://doi.org/10.3390/BiTaP-12782 - 29 Jun 2022
Viewed by 703
Abstract
Cytochrome c (Cc) is well-known as an electron carrier at mitochondria but can also catalyze peroxidase-like reactions. Although the reported catalytic abilities are low, the role of Cc in transforming environmental toxicants requires additional studies. We employed cardiolipin vesicles to [...] Read more.
Cytochrome c (Cc) is well-known as an electron carrier at mitochondria but can also catalyze peroxidase-like reactions. Although the reported catalytic abilities are low, the role of Cc in transforming environmental toxicants requires additional studies. We employed cardiolipin vesicles to stimulate the enzymatic activity of Cc and tested the catalytic system towards the dye methyl orange and the polycyclic aromatic hydrocarbons (PAHs) benzo[b]fluoranthene and benzo[a]pyrene. The results showed that cardiolipin-containing vesicles promoted dye decolorization and the oxidation of both PAHs by Cc, indicating that lipid membranes can be useful to further investigate Cc–mediated metabolism of toxicants. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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5 pages, 1044 KiB  
Proceeding Paper
Oxidative Stress and Inflammatory Response of Skin Fibroblasts Exposed to Chlorpyrifos
Med. Sci. Forum 2022, 11(1), 7; https://doi.org/10.3390/BiTaP-12791 - 13 Jul 2022
Viewed by 713
Abstract
Chlorpyrifos (CPF) is a widely used insecticide. The aim of this work was to study the effect of CPF in skin fibroblasts exposed to concentrations detected in human skin and unleash underlying cellular mechanisms. Fibroblasts were exposed to different concentrations (0.36–250 µM) of [...] Read more.
Chlorpyrifos (CPF) is a widely used insecticide. The aim of this work was to study the effect of CPF in skin fibroblasts exposed to concentrations detected in human skin and unleash underlying cellular mechanisms. Fibroblasts were exposed to different concentrations (0.36–250 µM) of CPF pure alone or in a commercial CPF mixture (Lethal 20) for 6 days. In conclusion, prolonged exposure to 250 µM of CPF pure and 125 µM of Lethal 20 caused a significant loss of the fibroblast´s viability. Moreover, the toxicity of this pesticide in fibroblasts is evidenced by the induction of oxidative stress and stimulation of the production of interleukin (IL)-6. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 584 KiB  
Proceeding Paper
Polyoxovanadates Contribution to Pharmacological, Antimicrobial and Toxicological Actions of Vanadium
Med. Sci. Forum 2022, 11(1), 8; https://doi.org/10.3390/BiTaP-12844 - 23 Jul 2022
Cited by 1 | Viewed by 986
Abstract
Studies of the pharmacological action of vanadium compounds have shown that vanadium has been arousing interest as a potential candidate for therapeutic applications. Polyoxovanadates (POVs) emerge from polyoxometalatates (POMs) and are responsible for an increase in the number of vanadium studies on multidirectional [...] Read more.
Studies of the pharmacological action of vanadium compounds have shown that vanadium has been arousing interest as a potential candidate for therapeutic applications. Polyoxovanadates (POVs) emerge from polyoxometalatates (POMs) and are responsible for an increase in the number of vanadium studies on multidirectional biological activity in view of their application in biomedicine. In fact, increasing research studies have shown POVs’ anti-bacterial, anti-fungal, anti-parasitic, anti-viral, anti-cancer as well as anti-diabetic activities. Herein, we highlight decavanadate and decavanadate compounds, perhaps the most studied POVs in biology, strengthening the potential use of such metallodrugs in the future. Thus, vanadium compounds, including POVs, show a great potential in the treatment of many types of diseases. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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5 pages, 790 KiB  
Proceeding Paper
Targeting Immune-Mediated Responses to Tackle GNE Myopathy
Med. Sci. Forum 2022, 11(1), 9; https://doi.org/10.3390/BiTaP-12788 - 07 Jul 2022
Viewed by 1165
Abstract
GNE myopathy (GNEM) is a rare disease clinically characterized by progressive muscle atrophy and weakness. Besides the rare incidence of the disease, the limited preclinical models are among the major bottlenecks for a better pathophysiological understanding of GNEM. This work aimed then at [...] Read more.
GNE myopathy (GNEM) is a rare disease clinically characterized by progressive muscle atrophy and weakness. Besides the rare incidence of the disease, the limited preclinical models are among the major bottlenecks for a better pathophysiological understanding of GNEM. This work aimed then at exploring the immunological context of GNEM in a recently established cell model. Our main findings suggest the involvement of an immune adaptive response, pointing to new alternative biological targets behind GNEM pathomechanisms. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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5 pages, 991 KiB  
Proceeding Paper
Potential Applications of Vanadium-Based Anticancer Drugs for Intratumoral Injections
Med. Sci. Forum 2022, 11(1), 10; https://doi.org/10.3390/BiTaP-12783 - 29 Jun 2022
Cited by 2 | Viewed by 952
Abstract
The administration of highly cytotoxic or immunomodulating drugs directly into a tumor is a method used in the clinic for late stages of cancers and in clinical trials for platinum-based drugs. A hydrophobic non-innocent Schiff base V(V) complex with a sterically hindered catecholate [...] Read more.
The administration of highly cytotoxic or immunomodulating drugs directly into a tumor is a method used in the clinic for late stages of cancers and in clinical trials for platinum-based drugs. A hydrophobic non-innocent Schiff base V(V) complex with a sterically hindered catecholate ligand was taken up rapidly into cancer cells and caused cell death as required for potential use as intratumoral agents. The synthesis was non-trivial on large scales and high purities. This class of complexes with sterically hindred catecholates is sufficiently stable to survive briefly under physiological conditions before hydrolysis and/or redox reactions. Degradation reactions occur very rapidly for complexes with less sterically hindered catacholates. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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4 pages, 588 KiB  
Proceeding Paper
Bioavailability and Biotransformation of Paralytic Shellfish Toxins Assessed by Permeability Assays Using Caco-2 Monolayers
Med. Sci. Forum 2022, 11(1), 11; https://doi.org/10.3390/BiTaP-12880 - 29 Jun 2022
Viewed by 616
Abstract
Caco-2 cells are well established models of intestinal epithelium, being routinely used to evaluate toxicity and bioavailability. Although usually overlooked, Caco-2 monolayers may also be used to assess biotransformation by epithelial cells, which may lead to significant changes in the composition and properties [...] Read more.
Caco-2 cells are well established models of intestinal epithelium, being routinely used to evaluate toxicity and bioavailability. Although usually overlooked, Caco-2 monolayers may also be used to assess biotransformation by epithelial cells, which may lead to significant changes in the composition and properties of the ingested matrix. In this work we characterize paralytic shellfish toxins (PSTs) extracted from the dinoflagellate Gymnodinium catenatum strain regarding their permeability through and biotransformation by polarized Caco-2 monolayers. The results show that biotransformation influences the apparent permeability measured for the different PSTs in the extract, and alters the extract’s effective toxicity. Full article
(This article belongs to the Proceedings of Biosystems in Toxicology and Pharmacology—Current Challenges)
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