High content analysis: A sensitive tool to detect and quantify the cytotoxic, synergistic and antagonistic effects of chemical contaminants in foods

Clarke, R. S. J.; Connolly, Lisa; Frizzell, Caroline; Elliott, Chris

doi:10.1016/j.toxlet.2015.01.011

Cited by 23 publications

(17 citation statements)

References 37 publications

(51 reference statements)

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“…In summary, most of the studies addressing the combined effect of OTA with other mycotoxins showed additive or synergistic interactions when binary mixtures were tested and data on multiple mixtures is very rare [ 110 ]. Since the publication of that review, a few more reports have been published and these are summarised below [ 203 , 204 , 205 , 206 , 207 ].…”

Section: Toxicity Of Mixtures Of Mycotoxinsmentioning

confidence: 99%

“…Binary combinations showed additive effects, whereas tertiary combinations of OTA, FB 1 and AFB 1 resulted in synergistic effects [ 207 ]. Further studies employed more sensitive high content analysis (HCA) resulting in synergistic interactions of binary mixtures of OTA and FB 1 [ 204 ]. In contrast, recent in vivo investigations by Corcuera et al of the combined toxicity of OTA and AFB 1 in orally exposed male F344 rats resulted in an antagonistic genotoxic interaction as tested via the micronucleus and comet assays [ 214 ].…”

Section: Toxicity Of Mixtures Of Mycotoxinsmentioning

confidence: 99%

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Comparative Ochratoxin Toxicity: A Review of the Available Data

Heussner

Bingle

2015

Toxins

253

147

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Ochratoxins are a group of mycotoxins produced by a variety of moulds. Ochratoxin A (OTA), the most prominent member of this toxin family, was first described by van der Merwe et al. in Nature in 1965. Dietary exposure to OTA represents a serious health issue and has been associated with several human and animal diseases including poultry ochratoxicosis, porcine nephropathy, human endemic nephropathies and urinary tract tumours in humans. More than 30 years ago, OTA was shown to be carcinogenic in rodents and since then extensive research has been performed in order to investigate its mode of action, however, this is still under debate. OTA is regarded as the most toxic family member, however, other ochratoxins or their metabolites and, in particular, ochratoxin mixtures or combinations with other mycotoxins may represent serious threats to human and animal health. This review summarises and evaluates current knowledge about the differential and comparative toxicity of the ochratoxin group.

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Section: Toxicity Of Mixtures Of Mycotoxinsmentioning

confidence: 99%

Section: Toxicity Of Mixtures Of Mycotoxinsmentioning

confidence: 99%

Comparative Ochratoxin Toxicity: A Review of the Available Data

Heussner

Bingle

2015

Toxins

253

147

View full text Add to dashboard Cite

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“…Previous work by the same authors has shown HCA as an important tool in determining the safety of food from single and complex mixtures of mycotoxins that are known to occur in many parts of the world (Clarke et al 2015). Futhermore, this is the first study to look at mycotoxin, heavy metal and pesticide mixtures with respect to their interactive cytotoxicity at levels of contamination found in foods.…”

Section: Introductionmentioning

confidence: 84%

Challenging conventional risk assessment with respect to human exposure to multiple food contaminants in food: A case study using maize.

Clarke¹,

Connolly²,

Frizzell³

et al. 2015

Toxicology Letters

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“…Studies using human hepatocytes have shown that HCS is more effective than past methods for identifying cytotoxic substances in humans [4]. The ability of HCS to quickly analyze the toxicological effects of a large number of compounds has also been confirmed in other studies, using various cell types, such as macrophages [9,10], human bronchial epithelial cells [10], human monocytes [11], intestinal epithelial cells [11], neuronal cell lines [12], lymphocytes [7], human osteosarcoma cells [13], and bovine kidney cells [14]. As a result of global acceptance of HCS technology in drug discovery and basic biomedical research [6], recent years have seen a growing number of reports dealing with the evaluation of the toxicity of various compounds, including drugs with known clinical hepatotoxicity profiles [15], fungal toxins occurring in foods [14], nanoparticles [16] and plant extracts [17,18].…”

Section: Introductionmentioning

confidence: 88%

A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis

Boncler

Golański

Łukasiak³

et al. 2017

PLoS ONE

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The toxicity of in vitro tested compounds is usually evaluated based on AC50 values calculated from dose-response curves. However, there is a large group of compounds for which a standard four-parametric sigmoid curve fitting may be inappropriate for estimating AC50. In the present study, 22 polyphenol-rich compounds were prioritized from the least to the most toxic based on the total area under and over the dose-response curves (AUOC) in relation to baselines. The studied compounds were ranked across three key cell indicators (mitochondrial membrane potential, cell membrane integrity and nuclear size) in a panel of five cell lines (HepG2, Caco-2, A549, HMEC-1, and 3T3), using a high-content screening (HCS) assay. Regarding AUOC score values, naringin (negative control) was the least toxic phenolic compound. Aronox, spent hop extract and kale leaf extract had very low cytotoxicity with regard to mitochondrial membrane potential and cell membrane integrity, as well as nuclear morphology (nuclear area). Kaempferol (positive control) exerted strong cytotoxic effects on the mitochondrial and nuclear compartments. Extracts from buckthorn bark, walnut husk and hollyhock flower were highly cytotoxic with regard to the mitochondrion and cell membrane, but not the nucleus. We propose an alternative algorithm for the screening of a large number of agents and for identifying those with adverse cellular effects at an early stage of drug discovery, using high content screening analysis. This approach should be recommended for series of compounds producing a non-sigmoidal cell response, and for agents with unknown toxicity or mechanisms of action.

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High content analysis: A sensitive tool to detect and quantify the cytotoxic, synergistic and antagonistic effects of chemical contaminants in foods

Cited by 23 publications

References 37 publications

Comparative Ochratoxin Toxicity: A Review of the Available Data

Comparative Ochratoxin Toxicity: A Review of the Available Data

Challenging conventional risk assessment with respect to human exposure to multiple food contaminants in food: A case study using maize.

A new approach for the assessment of the toxicity of polyphenol-rich compounds with the use of high content screening analysis

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