Acutoxbase, an innovative database for in vitro acute toxicity studies

Kinsner‐Ovaskainen, Agnieszka; Rzepka, Rafał; Rudowski, Robert; Coecke, Sandra; Cole, Thomas; Prieto, Pilar

doi:10.1016/j.tiv.2008.12.019

Cited by 35 publications

(13 citation statements)

References 12 publications

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“…In particular, Acutoxbase (Kinsner-Ovaskainen et al, 2009) is being database developed in the context of the EU FP6 project 'A-Cute-Tox' (www.acutetox.org), which aims to optimise and "pre-validate" an in vitro testing strategy for predicting acute human toxicity. At present, Acutoxbase is accessible only to the partners of the A-Cute-Tox project, but it is foreseen that (part of) the database will be placed in the public domain after the project is completed (July 2010 (Zhu et al, 2009a,b).…”

Section: Databasesmentioning

confidence: 99%

Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment

2010

EFSA Supporting Publications

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Section: Databasesmentioning

confidence: 99%

Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment

2010

EFSA Supporting Publications

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“…We selected eight test chemicals with different mechanisms of action from the reference compounds employed by the A-CuteTox in vitro testing project, including the neurotoxicity work package (WP7.1; Table 1); these agents ranged from relatively potent neurotoxins (acrylamide. atropine) to nonneurotoxins (rifampicin, verapamil) (Woehrling et al 2010;Kinsner-Ovaskainen et al 2009;Forsby and Blaauboer 2007). A number of approaches can be applied to discriminate between neuronal and astrocytic cell death, the most basic and time consuming being manual cell counting (Anderl et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

et al. 2010

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The timeline imposed by recent worldwide chemical legislation is not amenable to conventional in vivo toxicity testing, requiring the development of rapid, economical in vitro screening strategies which have acceptable predictive capacities. When acquiring regulatory neurotoxicity data, distinction on whether a toxic agent affects neurons and/or astrocytes is essential. This study evaluated neurofilament (NF) and glial fibrillary acidic protein (GFAP) directed single-cell (S-C) ELISA and flow cytometry as methods for distinguishing cell-specific cytoskeletal responses, using the established human NT2 neuronal/astrocytic (NT2.N/A) co-culture model and a range of neurotoxic (acrylamide, atropine, caffeine, chloroquine, nicotine) and non-neurotoxic (chloramphenicol, rifampicin, verapamil) test chemicals. NF and GFAP directed flow cytometry was able to identify several of the test chemicals as being specifically neurotoxic (chloroquine, nicotine) or astrocytoxic (atropine, chloramphenicol) via quantification of cell death in the NT2.N/A model at cytotoxic concentrations using the resazurin cytotoxicity assay. Those neurotoxicants with low associated cytotoxicity are the most significant in terms of potential hazard to the human nervous system. The NF and GFAP directed S-C ELISA data predominantly demonstrated the known neurotoxicants only to affect the neuronal and/or astrocytic cytoskeleton in the NT2.N/A cell model at concentrations below those affecting cell viability. This report concluded that NF and GFAP directed S-C ELISA and flow cytometric methods may prove to be valuable additions to an in vitro screening strategy for differentiating cytotoxicity from specific neuronal and/or astrocytic toxicity. Further work using the NT2.N/A model and a broader array of toxicants is appropriate in order to confirm the applicability of these methods.

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“…The LUCS procedure described for chloroquine was applied to 52 other substances taken from the ACuteTox EU program 12 and covering a large spectrum of origins (drugs, toxins, pesticides, food additives,…). Monographs of the 53 substances assayed by LUCS are given in Fig.…”

Section: Resultsmentioning

confidence: 99%

LUCS (Light-Up Cell System), a universal high throughput assay for homeostasis evaluation in live cells

Derick

Gironde

Pério

et al. 2017

Sci Rep

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Observations of fluorescent cyanine dye behavior under illumination at 500 nm lead to a novel concept in cell biology allowing the development of a new live cell assay called LUCS, for Light-Up Cell System, measuring homeostasis in live cells. Optimization of the LUCS process resulted in a standardized, straightforward and high throughput assay with applications in toxicity assessment. The mechanisms of the LUCS process were investigated. Electron Paramagnetic Resonance experiments showed that the singlet oxygen and hydroxyl radical are involved downstream of the light effect, presumably leading to deleterious oxidative stress that massively opens access of the dye to its intracellular target. Reversible modulation of LUCS by both verapamil and proton availability indicated that plasma membrane proton/cation antiporters, possibly of the MATE drug efflux transport family, are involved. A mechanistic model is presented. Our data show that intracellular oxidation can be controlled by tuning light energy, opening applications in regulatory purposes, anti-oxidant research, chemotherapy efficacy and dynamic phototherapy strategies.

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Acutoxbase, an innovative database for in vitro acute toxicity studies

Cited by 35 publications

References 12 publications

Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment

Applicability of QSAR analysis to the evaluation of the toxicological relevance of metabolites and degradates of pesticide active substances for dietary risk assessment

Single-Cell ELISA and Flow Cytometry as Methods for Highlighting Potential Neuronal and Astrocytic Toxicant Specificity

LUCS (Light-Up Cell System), a universal high throughput assay for homeostasis evaluation in live cells

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