Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Kupke, Franziska; Herz, Corinna; Hanschen, Franziska S.; Platz, Stefanie; Odongo, Grace Akinyi; Helmig, Simone; Rodríguez, Maria M.; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

doi:10.1038/srep37631

Cited by 32 publications

(12 citation statements)

References 36 publications

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“…All values were calculated on the basis of data given in Table 2 − 0.47), but rather to nitriles (Pearson coefficient − 0.88). This result contrasts other recent reports, which suggest that mainly ITC are responsible for cytotoxicity in in vitro [64] and in vivo models [65]. Recently, it was shown that the differences in HPLC fingerprints obtained for cruciferous plant extracts, indicating the presence of different chemical constituents, were mirrored by the varying antiproliferative activity against the HCT116 cell line [66].…”

Section: Cytotoxicitycontrasting

confidence: 84%

Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables

Kołodziejski

Piekarska

Hanschen

et al. 2018

Eur Food Res Technol

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The studies on the characterisation of glucosinolates (GLs) and their breakdown products in Brassicaceae species focus mainly on the edible parts. However, other products, e.g., dietary supplements, may be produced also from non-edible parts such as roots or early forms of growth: seeds or sprouts. Biological activity of these products depends on quantitative and qualitative GL composition, but is also strictly determined by GL conversion rate to chemopreventive isothiocyanates (ITC) and indoles. The aim of this study was to evaluate the conversion rate of GLs to ITC and indoles for various plant parts of chosen Brassica species in relation to their biological activity. For this purpose, the composition of GLs and their degradation products was determined as well as activity of myrosinase. Toxicological part of studies involved: MTT assay, restriction analysis, comet assay and Ames test. The composition of GLs and conversion rate to ITC and indoles was found to differ significantly between Brassica species and individual parts of the plant. The highest efficiency of conversion was observed for edible parts of plants: more than 70%, while in sprouts, it reached less than 1%, though myrosinase activity did not differ. The conversion rate directly affected biological activity of plant material. Higher concentration of ITC/indoles in the sample led to the increase of cytotoxicity. Majority of tested samples were able to induce covalent DNA modification in cell-free system. It was also confirmed that the presence of indolic GLs and products of their degradation stimulated mutagenicity, but did not lead to DNA fragmentation in cultured cells.

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Section: Cytotoxicitycontrasting

confidence: 84%

Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables

Kołodziejski

Piekarska

Hanschen

et al. 2018

Eur Food Res Technol

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“…Isolation of hepatocytes was performed as described before (21, 22). For in vitro stimulations, 12-well plates were coated with collagen 24 h prior to cultivation.…”

Section: Methodsmentioning

confidence: 99%

Organ-Specific Expression of IL-1 Receptor Results in Severe Liver Injury in Type I Interferon Receptor Deficient Mice

et al. 2019

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Upon treatment with polyinosinic:polycytidylic acid [poly(I:C)], an artificial double-stranded RNA, type I interferon receptor-deficient (IFNAR −/− ) mice develop severe liver injury seen by enhanced alanine aminotransferase (ALT) activity in the serum that is not observed in their wildtype (WT) counterparts. Recently, we showed that liver injury is mediated by an imbalanced expression of interleukin (IL)-1β and its receptor antagonist (IL1-RA) in the absence of type I IFN. Here we show that despite comparable expression levels of IL-1β in livers and spleens, spleens of poly(I:C)-treated IFNAR −/− mice show no signs of injury. In vitro analyses of hepatocytes and splenocytes revealed that poly(I:C) had no direct toxic effect on hepatocytes. Furthermore, expression levels of cytokines involved in other models for liver damage or protection such as interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-6, IL-10, IL-17, and IL-22 were comparable for both organs in WT and IFNAR −/− mice upon treatment. Moreover, flow cytometric analyses showed that the composition of different immune cells in livers and spleens were not altered upon injection of poly(I:C). Finally, we demonstrated that the receptor binding IL-1β, IL1R1, is specifically expressed in livers but not spleens of WT and IFNAR −/− mice. Accordingly, mice double-deficient for IFNAR and IL1R1 developed no liver injury upon poly(I:C) treatment and showed ALT activities comparable to those of WT mice. Collectively, liver injury is mediated by the organ-specific expression of IL1R1 in the liver.

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“…On the other hand, a fourth class of specifier proteins, namely the thiocyanate-forming protein (TFP), was reported to catalyse the formation of benzylthiocyanate in Lepidium sativum 25. As many Brassica vegetables, among them broccoli, cabbage and pak choi, contain ESP, nitriles and EPTs instead of ITCs can be the resultant main breakdown products142627. Moreover, many Brassica vegetables are thermally processed prior to consumption and this changes ITC formation dramatically.…”

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confidence: 99%

Optimizing isothiocyanate formation during enzymatic glucosinolate breakdown by adjusting pH value, temperature and dilution in Brassica vegetables and Arabidopsis thaliana

Hanschen

Oliviero

Schreiner

et al. 2017

Sci Rep

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101

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Consumption of glucosinolate-rich Brassicales vegetables is associated with a decreased risk of cancer with enzymatic hydrolysis of glucosinolates playing a key role. However, formation of health-promotingisothiocyanates is inhibited by the epithiospecifier protein in favour of nitriles and epithionitriles. Domestic processing conditions, such as changes in pH value, temperature or dilution, might also affect isothiocyanate formation. Therefore, the influences of these three factors were evaluated in accessions of Brassica rapa, Brassica oleracea, and Arabidopsis thaliana. Mathematical modelling was performed to determine optimal isothiocyanate formation conditions and to obtain knowledge on the kinetics of the reactions. At 22 °C and endogenous plant pH, nearly all investigated plants formed nitriles and epithionitriles instead of health-promoting isothiocyanates. Response surface models, however, clearly demonstrated that upon change in pH to domestic acidic (pH 4) or basic pH values (pH 8), isothiocyanate formation considerably increases. While temperature also affects this process, the pH value has the greatest impact. Further, a kinetic model showed that isothiocyanate formation strongly increases due to dilution. Finally, the results show that isothiocyanate intake can be strongly increased by optimizing the conditions of preparation of Brassicales vegetables.Brassicales plants, including Arabidopsis thaliana, broccoli, cabbage and pak choi contain glucosinolates (GLSs). These sulphur-containing secondary plant metabolites not only play an important role in the plant's defense against biotic stressors, but also affect the taste of these vegetables and contribute to human health 1 . To date, a total of 130 GLSs have been identified that can be subdivided according to the structure of their variable side chain into the group of aliphatic, aromatic or indole GLS 2 . These plant metabolites are stored in the plant vacuole or in specialized S-cells 3 , but upon cell disruption, they encounter the endogenous GLS-hydrolysing enzyme myrosinase, a β-d-thioglucosidase, and the GLSs will be hydrolysed to release isothiocyanates (ITCs), nitriles and epithionitriles (EPTs) 4 . Due to their electrophilicity, GLSs in general and ITCs in particular act as effective deterrents against a multitude of pathogens as these compounds have antifungal, antimicrobial as well as insecticidal properties [5][6][7] . For humans, ITCs, such as the 4-(methylsulphinyl)butyl ITC (4MSOB-ITC), exert a multitude of health beneficial effects, including antimicrobial, antiinflammatory, antithrombotic and chemopreventive effects [8][9][10]

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Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Cited by 32 publications

References 36 publications

Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables

Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables

Organ-Specific Expression of IL-1 Receptor Results in Severe Liver Injury in Type I Interferon Receptor Deficient Mice

Optimizing isothiocyanate formation during enzymatic glucosinolate breakdown by adjusting pH value, temperature and dilution in Brassica vegetables and Arabidopsis thaliana

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