Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling

Kiwamoto, R.; Ploeg, D. A. Ver; Rietjens, Ivonne M.C.M.; Punt, Ans

doi:10.1016/j.tiv.2015.11.014

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…Furthermore, in addition to identifying vanillin as potentially highly toxic, we also identified—using this screen—3 e-liquids that contain diacetyl (2,3-butanedione), which causes bronchiolitis obliterans, and 5 e-liquids that contain 2,3-butanedione monooxime, which is a chemical diphosphatase that blocks ATP-sensitive K + channels [ 46 – 51 ]. Interestingly, many flavors, e.g., benzaldehyde (almond) and cinnamaldehyde (cinnamon), are aldehydes that can form protein adducts [ 52 ]. Benzaldehyde was only detected in 4 e-liquids.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

et al. 2018

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The e-liquids used in electronic cigarettes (E-cigs) consist of propylene glycol (PG), vegetable glycerin (VG), nicotine, and chemical additives for flavoring. There are currently over 7,700 e-liquid flavors available, and while some have been tested for toxicity in the laboratory, most have not. Here, we developed a 3-phase, 384-well, plate-based, high-throughput screening (HTS) assay to rapidly triage and validate the toxicity of multiple e-liquids. Our data demonstrated that the PG/VG vehicle adversely affected cell viability and that a large number of e-liquids were more toxic than PG/VG. We also performed gas chromatography–mass spectrometry (GC-MS) analysis on all tested e-liquids. Subsequent nonmetric multidimensional scaling (NMDS) analysis revealed that e-liquids are an extremely heterogeneous group. Furthermore, these data indicated that (i) the more chemicals contained in an e-liquid, the more toxic it was likely to be and (ii) the presence of vanillin was associated with higher toxicity values. Further analysis of common constituents by electron ionization revealed that the concentration of cinnamaldehyde and vanillin, but not triacetin, correlated with toxicity. We have also developed a publicly available searchable website (www.eliquidinfo.org). Given the large numbers of available e-liquids, this website will serve as a resource to facilitate dissemination of this information. Our data suggest that an HTS approach to evaluate the toxicity of multiple e-liquids is feasible. Such an approach may serve as a roadmap to enable bodies such as the Food and Drug Administration (FDA) to better regulate e-liquid composition.

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Section: Discussionmentioning

confidence: 99%

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

et al. 2018

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“…According to Kiwamoto et al, 33 unlike many α,β-unsaturated aldehydes, cinnamaldehyde is not genotoxic or carcinogenic in vivo. These authors compared DNA-adduct formation (eq 1) of cinnamaldehyde and 18 foodborne α,β-unsaturated aldehydes using physiologically based kinetic/dynamic (PBK/D) modeling in rats.…”

Section: ■ Introductionmentioning

confidence: 99%

Chemistry, Antimicrobial Mechanisms, and Antibiotic Activities of Cinnamaldehyde against Pathogenic Bacteria in Animal Feeds and Human Foods

Friedman

2017

J. Agric. Food Chem.

173

111

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Cinnamaldehyde is a major constituent of cinnamon essential oils produced by aromatic cinnamon plants. This compound has been reported to exhibit antimicrobial properties in vitro in laboratory media and in animal feeds and human foods contaminated with disease-causing bacteria including Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. This integrated review surveys and interprets our current knowledge of the chemistry, analysis, safety, mechanism of action, and antibiotic activities of cinnamaldehyde in food animal (cattle, lambs, calves, pigs, poultry) diets and in widely consumed liquid (apple, carrot, tomato, and watermelon juices, milk) and solid foods. Solid foods include various fruits (bayberries, blueberries, raspberries, and strawberries), vegetables (carrots, celery, lettuce, spinach, cucumbers, and tomatoes), meats (beef, ham, pork, and frankfurters), poultry (chickens and turkeys), seafood (oysters and shrimp), bread, cheese, eggs, infant formula, and peanut paste. The described findings are not only of fundamental interest but also have practical implications for food safety, nutrition, and animal and human health. The collated information and suggested research needs will hopefully facilitate and guide further studies needed to optimize the use of cinnamaldehyde alone and in combination with other natural antimicrobials and medicinal antibiotics to help prevent and treat food animal and human diseases.

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“…The detoxification efficiency and reaction efficiency with DNA vary depending on the structure [ 40 ]. Kiwamoto et al demonstrated that although cinnamaldehyde induces a higher DNA adduct level than other α,β-unsaturated aldehydes, this level is three orders of magnitude lower than the natural background levels of structurally similar DNA adducts observed in the human liver, i.e., the observed level does not show mutagenicity [ 41 ]. Indeed, most α,β-unsaturated aldehydes may be of no concern in terms of mutagenicity and carcinogenicity in vivo.…”

Section: Discussionmentioning

confidence: 99%

In vivo and in vitro mutagenicity of perillaldehyde and cinnamaldehyde

et al. 2021

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Background Perillaldehyde and cinnamaldehyde are natural substances found in plants that are used as flavoring ingredients. Due to the α,β-unsaturated aldehydes in their structures, these compounds are expected to be DNA reactive. Indeed, several reports have indicated that perillaldehyde and cinnamaldehyde show positive in in vitro and in vivo genotoxicity tests. However, their genotoxic potentials are currently disputed. To clarify the mutagenicity of perillaldehyde and cinnamaldehyde, we conducted in silico quantitative structure–activity relationship (QSAR) analysis, in vitro Ames tests, and in vivo transgenic rodent gene mutation (TGR) assays. Results In Ames tests, perillaldehyde was negative and cinnamaldehyde was positive; these respective results were supported by QSAR analysis. In TGR assays, we treated Muta™ Mice with perillaldehyde and gpt-delta mice with cinnamaldehyde up to the maximum tested doses (1000 mg/kg/day). There was no increase in gene mutations in the liver, glandular stomach, or small intestine following all treatments except the positive control (N-ethyl-N-nitrosourea at 100 mg/kg/day). Conclusions These data clearly show no evidence of in vivo mutagenic potentials of perillaldehyde and cinnamaldehyde (administered up to 1000 mg/kg/day) in mice; however, cinnamaldehyde is mutagenic in vitro.

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Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling

Cited by 8 publications

References 38 publications

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

Evaluation of e-liquid toxicity using an open-source high-throughput screening assay

Chemistry, Antimicrobial Mechanisms, and Antibiotic Activities of Cinnamaldehyde against Pathogenic Bacteria in Animal Feeds and Human Foods

In vivo and in vitro mutagenicity of perillaldehyde and cinnamaldehyde

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