scholarly journals Cell-based in vitro models in environmental toxicology: a review

Biomonitoring ◽  
2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Michael Poteser
Keyword(s):  
Cultured Cells ◽  
Biological Effects ◽  
Epidemiological Data ◽  
In Vitro Models ◽  
Environmental Toxicology ◽  
In Vitro Assays ◽  
Cellular Effects ◽  
Potential Risks ◽  
Cellular Pathways

AbstractAn analysis of biological effects induced by environmental toxins and exposure-related evaluation of potential risks for health and environment represent central tasks in classical biomonitoring. While epidemiological data and population surveys are clearly the methodological frontline of this scientific field, cellbased in vitro assays provide information on toxin-affected cellular pathways and mechanisms, and are important sources for the identification of relevant biomarkers. This review provides an overview on currently available in vitro methods based on cultured cells, as well as some limitations and considerations that are of specific interest in the context of environmental toxicology. Today, a large number of different endpoints can be determined to pinpoint basal and specific toxicological cellular effects. Technological progress and increasingly refined protocols are extending the possibilities of cell-based in vitro assays in environmental toxicology and promoting their increasingly important role in biomonitoring.

scholarly journals Lignans from Bursera fagaroides Affect In Vivo Cell Behavior by Disturbing the Tubulin Cytoskeleton in Zebrafish Embryos

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 8 ◽  
Author(s):  
Mayra Antúnez-Mojica ◽  
Andrés Rojas-Sepúlveda ◽  
Mario Mendieta-Serrano ◽  
Leticia Gonzalez-Maya ◽  
Silvia Marquina ◽  
...  
Keyword(s):  
Cell Migration ◽  
Biological Effects ◽  
In Vitro Models ◽  
In Vivo Model ◽  
Zebrafish Embryos ◽  
Microtubule Cytoskeleton ◽  
Zebrafish Model ◽  
Bioassay Guided Fractionation

By using a zebrafish embryo model to guide the chromatographic fractionation of antimitotic secondary metabolites, seven podophyllotoxin-type lignans were isolated from a hydroalcoholic extract obtained from the steam bark of Bursera fagaroides. The compounds were identified as podophyllotoxin (1), β-peltatin-A-methylether (2), 5′-desmethoxy-β-peltatin-A-methylether (3), desmethoxy-yatein (4), desoxypodophyllotoxin (5), burseranin (6), and acetyl podophyllotoxin (7). The biological effects on mitosis, cell migration, and microtubule cytoskeleton remodeling of lignans 1–7 were further evaluated in zebrafish embryos by whole-mount immunolocalization of the mitotic marker phospho-histone H3 and by a tubulin antibody. We found that lignans 1, 2, 4, and 7 induced mitotic arrest, delayed cell migration, and disrupted the microtubule cytoskeleton in zebrafish embryos. Furthermore, microtubule cytoskeleton destabilization was observed also in PC3 cells, except for 7. Therefore, these results demonstrate that the cytotoxic activity of 1, 2, and 4 is mediated by their microtubule-destabilizing activity. In general, the in vivo and in vitro models here used displayed equivalent mitotic effects, which allows us to conclude that the zebrafish model can be a fast and cheap in vivo model that can be used to identify antimitotic natural products through bioassay-guided fractionation.

scholarly journals Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer’s Disease Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1626
Author(s):  
Line Séguy ◽  
Léna Guyon ◽  
Manon Maurel ◽  
Pascal Verdié ◽  
Audrey Davis ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vitro Assays ◽  
Titration Calorimetry ◽  
Therapeutic Effects ◽  
Disease Treatment ◽  
Cellular Effects ◽  
Irritable Bowel ◽  
The Stability

Background and Purpose: The activation of 5-HT4 receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer’s disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood–brain barrier shuttle peptide. Results: The butyrylcholinesterase inhibitory activity of tegaserod and its neuroprotective cellular effects were highlighted, confirming the interest of this pleiotropic drug for AD treatment. In regard to its drugability profile, and in order to limit its peripheral distribution after IV administration, its encapsulation into monodisperse lipid nanoemulsions (Tg-NEs) of about 50 nm, and with neutral zeta potential characteristics, was performed. The stability of the formulation in stock conditions at 4 °C and in blood biomimetic medium was established. The adsorption on Tg-NEs of peptide-22 was realized. The functionalized NEs were characterized by chromatographic methods (SEC and C18/HPLC) and isothermal titration calorimetry, attesting the efficiency of the adsorption. From in vitro assays, these nanocarriers appeared suitable for enabling tegaserod controlled release without hemolytic properties. Conclusion: The developed peptide-22 functionalized Tg-NEs appear as a valuable tool to allow exploration of the repurposed tegaserod in AD treatment in further preclinical studies.

scholarly journals A Next-Generation Risk Assessment Case Study for Coumarin in Cosmetic Products

2020 ◽  
Vol 176 (1) ◽  
pp. 236-252 ◽  
Author(s):  
Maria T Baltazar ◽  
Sophie Cable ◽  
Paul L Carmichael ◽  
Richard Cubberley ◽  
Tom Cull ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Next Generation ◽  
Animal Testing ◽  
Immunomodulatory Effects ◽  
Margin Of Safety

Abstract Next-Generation Risk Assessment is defined as an exposure-led, hypothesis-driven risk assessment approach that integrates new approach methodologies (NAMs) to assure safety without the use of animal testing. These principles were applied to a hypothetical safety assessment of 0.1% coumarin in face cream and body lotion. For the purpose of evaluating the use of NAMs, existing animal and human data on coumarin were excluded. Internal concentrations (plasma Cmax) were estimated using a physiologically based kinetic model for dermally applied coumarin. Systemic toxicity was assessed using a battery of in vitro NAMs to identify points of departure (PoDs) for a variety of biological effects such as receptor-mediated and immunomodulatory effects (Eurofins SafetyScreen44 and BioMap Diversity 8 Panel, respectively), and general bioactivity (ToxCast data, an in vitro cell stress panel and high-throughput transcriptomics). In addition, in silico alerts for genotoxicity were followed up with the ToxTracker tool. The PoDs from the in vitro assays were plotted against the calculated in vivo exposure to calculate a margin of safety with associated uncertainty. The predicted Cmax values for face cream and body lotion were lower than all PoDs with margin of safety higher than 100. Furthermore, coumarin was not genotoxic, did not bind to any of the 44 receptors tested and did not show any immunomodulatory effects at consumer-relevant exposures. In conclusion, this case study demonstrated the value of integrating exposure science, computational modeling and in vitro bioactivity data, to reach a safety decision without animal data.

scholarly journals Evaluation of the Biocompatibility and Endothelial Differentiation Capacity of Mesenchymal Stem Cells by Polyethylene Glycol Nanogold Composites

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4265
Author(s):  
Huey-Shan Hung ◽  
Yi-Chin Yang ◽  
Wei-Chien Kao ◽  
Chun-An Yeh ◽  
Kai-Bo Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Polyethylene Glycol ◽  
Au Nanoparticles ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Endothelial Differentiation ◽  
Vascular Regeneration

Cardiovascular Diseases (CVDs) such as atherosclerosis, where inflammation occurs in the blood vessel wall, are one of the major causes of death worldwide. Mesenchymal Stem Cells (MSCs)-based treatment coupled with nanoparticles is considered to be a potential and promising therapeutic strategy for vascular regeneration. Thus, angiogenesis enhanced by nanoparticles is of critical concern. In this study, Polyethylene Glycol (PEG) incorporated with 43.5 ppm of gold (Au) nanoparticles was prepared for the evaluation of biological effects through in vitro and in vivo assessments. The physicochemical properties of PEG and PEG–Au nanocomposites were first characterized by UV-Vis spectrophotometry (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and Atomic Force Microscopy (AFMs). Furthermore, the reactive oxygen species scavenger ability as well as the hydrophilic property of the nanocomposites were also investigated. Afterwards, the biocompatibility and biological functions of the PEG–Au nanocomposites were evaluated through in vitro assays. The thin coating of PEG containing 43.5 ppm of Au nanoparticles induced the least platelet and monocyte activation. Additionally, the cell behavior of MSCs on PEG–Au 43.5 ppm coating demonstrated better cell proliferation, low ROS generation, and enhancement of cell migration, as well as protein expression of the endothelialization marker CD31, which is associated with angiogenesis capacity. Furthermore, anti-inflammatory and endothelial differentiation ability were both evaluated through in vivo assessments. The evidence demonstrated that PEG–Au 43.5 ppm implantation inhibited capsule formation and facilitated the expression of CD31 in rat models. TUNEL assay also indicated that PEG–Au nanocomposites would not induce significant cell apoptosis. The above results elucidate that the surface modification of PEG–Au nanomaterials may enable them to serve as efficient tools for vascular regeneration grafts.

scholarly journals The Microtubule Plus-End Proteins EB1 and Dynactin Have Differential Effects on Microtubule Polymerization

2003 ◽  
Vol 14 (4) ◽  
pp. 1405-1417 ◽  
Author(s):  
Lee A. Ligon ◽  
Spencer S. Shelly ◽  
Mariko Tokito ◽  
Erika L.F. Holzbaur
Keyword(s):  
Cultured Cells ◽  
Cell Types ◽  
Microtubule Dynamics ◽  
In Vitro Assays ◽  
Nucleation Effect ◽  
Microtubule Polymerization ◽  
The Individual ◽  
Different Cell Types ◽  
Dynactin Complex

Several microtubule-binding proteins including EB1, dynactin, APC, and CLIP-170 localize to the plus-ends of growing microtubules. Although these proteins can bind to microtubules independently, evidence for interactions among them has led to the hypothesis of a plus-end complex. Here we clarify the interaction between EB1 and dynactin and show that EB1 binds directly to the N-terminus of the p150Glued subunit. One function of a plus-end complex may be to regulate microtubule dynamics. Overexpression of either EB1 or p150Glued in cultured cells bundles microtubules, suggesting that each may enhance microtubule stability. The morphology of these bundles, however, differs dramatically, indicating that EB1 and dynactin may act in different ways. Disruption of the dynactin complex augments the bundling effect of EB1, suggesting that dynactin may regulate the effect of EB1 on microtubules. In vitro assays were performed to elucidate the effects of EB1 and p150Glued on microtubule polymerization, and they show that p150Gluedhas a potent microtubule nucleation effect, whereas EB1 has a potent elongation effect. Overall microtubule dynamics may result from a balance between the individual effects of plus-end proteins. Differences in the expression and regulation of plus-end proteins in different cell types may underlie previously noted differences in microtubule dynamics.

scholarly journals A retrospective analysis to explore the applicability of fish biomarkers and sediment bioassays along contaminated salinity transects

2009 ◽  
Vol 66 (10) ◽  
pp. 2089-2105 ◽  
Author(s):  
Cor A. Schipper ◽  
Joost Lahr ◽  
Paul J. van den Brink ◽  
Steve G. George ◽  
Peter-Diedrich Hansen ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Large Scale ◽  
Biological Effects ◽  
In Vitro Assays ◽  
Multivariate Statistical ◽  
Large Scale Field ◽  
Hepatic Metallothionein ◽  
Fish Biomarkers

Abstract Schipper, C. A., Lahr, J., van den Brink, P. J., George, S. G., Hansen, P-D., da Silva de Assis, H. C., van der Oost, R., Thain, J. E., Livingstone, D., Mitchelmore, C., van Schooten, F-J., Ariese, F., Murk, A. J., Grinwis, G. C. M., Klamer, H., Kater, B. J., Postma, J. F., van der Werf, B., and Vethaak, A. D. 2009. A retrospective analysis to explore the applicability of fish biomarkers and sediment bioassays along contaminated salinity transects. – ICES Journal of Marine Science, 66: 2089–2105. Biological-effects monitoring in estuarine environments is complex as a result of strong gradients and fluctuations in salinity and other environmental conditions, which may influence contaminant bioavailability and the physiology and metabolism of the organisms. To select the most robust and reliable biological-effect methods for monitoring and assessment programmes, a large-scale field study was conducted in two estuarine transects in the Netherlands. The locations ranged from heavily polluted harbour areas (the ports of Rotterdam and Amsterdam) to cleaner coastal and freshwater sites. Assessment methods used included a variety of biomarkers in flounder (Platichthys flesus) and a range of in vitro (sediment extracts) and in vivo bioassays. Multivariate statistical analysis was applied to investigate correlations and relationships between various biological effects and contaminant levels in flounder liver or sediments. Several biological methods seemed to be too much affected by salinity differences for routine use in estuaries. The most discriminative biomarkers in the study were hepatic metallothionein content and biliary 1-OH pyrene in fish. Mechanism-based in vitro assays DR-CALUX and ER-CALUX applied to sediment extracts for screening of potential toxicity were much more responsive than in vivo bioassays with macro-invertebrates using survival as an endpoint.

In Vitro Models That Support Adhesion Specificity in Biofilms of Oral Bacteria

1997 ◽  
Vol 11 (1) ◽  
pp. 33-42 ◽  
Author(s):  
R.P. Ellen ◽  
G. Lépine ◽  
P.-M. Nghiem
Keyword(s):  
Matrix Protein ◽  
Protein S ◽  
Specific Protein ◽  
In Vitro Models ◽  
Oral Bacteria ◽  
Host Cells ◽  
In Vitro Assays ◽  
Covalent Bonds ◽  
Enzyme Substrate Recognition

Adhesion to adsorbed pellicles and interspecies co-adhesion to form plaque biofilms involve selective interactions of bacterial adhesins with specific receptors. Our laboratory has devised in vitro assays for co-adhesion between Actinomyces naeslundii and Streptococcus oralis or Porphyromonas gingivalis on saliva-coated mineral and hexadecane droplet substrata. P. gingivalis structures significant for co-adhesion with A. naeslundii include surface vesicles and fimbriae. A family of arginine-specific cysteine proteinases in vesicles may be involved in adherence to bacteria, to host cells, and to matrix proteins. New research from several laboratories has found that such proteinases are processed from genes encoding polyproteins containing both proteinase and hemagglutinin domains. In addition to enzyme-substrate recognition, bacterial adhesion is often determined by specific protein-peptide and lectin-carbohydrate recognition. A. naeslundii - salivary proline-rich protein, S. gordonii - salivary a-amylase, and Treponema denticola - matrix protein recognition are examples of the former. Co-adhesion of A. naeslundii and S. oralis is an example of the latter. Lactose can selectively desorb A. naeslundii cells from mixed biofilms with S. oralis, a demonstration of the significance of specificity. Although non-specific forces are probably secondary to stereochemical fit in determining the selective range of surfaces that bacteria have evolved to recognize and bind, they probably help stabilize non-covalent bonds within aligned, complementary domains.

Environmental Toxicology Assays Using Organ-on-Chip

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Patarajarin Akarapipad ◽  
Kattika Kaarj ◽  
Yan Liang ◽  
Jeong-Yeol Yoon
Keyword(s):  
Drug Toxicity ◽  
Environmental Toxicology ◽  
In Vitro Assays ◽  
Annual Review ◽  
Publication Date ◽  
Environmental Toxicants ◽  
Toxicity Screening ◽  
On Chip

Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 14 is August 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Comparison of in Vitro Models for the Prediction of Compound Absorption across the Human Intestinal Mucosa

2004 ◽  
Vol 9 (7) ◽  
pp. 598-606 ◽  
Author(s):  
Silvia Miret ◽  
Leo Abrahamse ◽  
Els M. de Groene
Keyword(s):  
Cell Differentiation ◽  
High Throughput ◽  
High Throughput Screening ◽  
In Vitro Models ◽  
Assay System ◽  
In Vitro Assays ◽  
Cell Models ◽  
Artificial Membrane ◽  
Permeability Assay

Several in vitro assays have been developed to evaluate the gastrointestinal absorption of compounds. Our aim was to compare 3 of these methods: 1) the bio-mimetic artificial membrane permeability assay (BAMPA) method, which offers a high-throughput, noncellular approach to the measurement of passive transport; 2) the traditional Caco-2 cell assay, the use of which as a high-throughput tool is limited by the long cell differentiation time (21 days); and 3) The BioCoat™ high-throughput screening Caco-2 Assay System, which reduces Caco-2 cell differentiation to 3 days. The transport of known compounds (such as cephalexin, propranolol, or chlorothiazide) was studied at pH 7.4 and 6.5 in BAMPA and both Caco-2 cell models. Permeability data obtained was correlated to known values of human absorption. Best correlations ( r = 0.9) were obtained at pH 6.5 for BAMPA and at pH 7.4 for the Caco-2 cells grown for 21 days. The Caco-2 BioCoat™ HTS Caco-2 Assay System does not seem to be adequate for the prediction of absorption. The overall results indicate that BAMPA and the 21-day Caco-2 system can be complementary for an accurate prediction of human intestinal absorption.

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