Enniatin B-induced cell death and inflammatory responses in RAW 267.4 murine macrophages

Gammelsrud, A.; Solhaug, Anita; Dendelé, Beatrice; Sandberg, Wiggo J.; Ivanova, Lada; Bølling, Anette Kocbach; Lagadic‐Gossmann, Dominique; Refsnes, Magne; Becher, Rune; Eriksen, Gunnar Sundstøl; Holme, Jørn A.

doi:10.1016/j.taap.2012.03.014

Cited by 61 publications

(56 citation statements)

References 58 publications

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“…For instance, when cells were exposed to 25 mM ENN B, the sub-G 0 population of H295R cells increased from 2.4, 0.5 and 1% in the control cells to 11, 24.6 and 32.2% after 24, 48 and 72 h, respectively. These results are in agreement with previous reports (Dornetshuber et al, 2007;Gammelsrud et al, 2012;Ivanova et al, 2012).…”

Section: [ ( F I G _ 3 ) T D $ F I G ]supporting

confidence: 94%

“…Chronic exposure by feeding experiments may induce feed refusal, weight loss and reduced productivity (Jestoi, 2008). However, there are several in vitro experiments showing that ENNs are cytotoxic at low micromolar concentrations (Ivanova et al, 2006;Dornetshuber et al, 2007;Behm et al, 2009;Meca et al, 2011;Gammelsrud et al, 2012). The primary toxicity of ENNs results from its ionophoric characteristics that enables transfer of mono-and divalent cations through cell membrane (Jestoi, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…The primary toxicity of ENNs results from its ionophoric characteristics that enables transfer of mono-and divalent cations through cell membrane (Jestoi, 2008). Moreover, ENN B also exerts cytotoxic activities by inducing mitochondrial modifications and cell cycle disruption, finally resulting in apoptotic cell death (Dornetshuber et al, 2007;Watjen et al, 2009;Gammelsrud et al, 2012). ENN B in concentrations up to 100 mM has not shown genotoxic activity (Behm et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays

et al. 2015

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Section: [ ( F I G _ 3 ) T D $ F I G ]supporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays

et al. 2015

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“…82,83 This is important as it was shown that, besides their well-known cytotoxic properties, 16,[84][85][86][87] the cyclic depsipeptide mycotoxins ENNs and BEA also exert effects on the immune system in general. So have Gammelsrud et al 88 shown that ENN B en BEA influenced the expression of various co-stimulatory molecules, indicating that ENN B as well as BEA, could disturb dendritic cell migration and interfere with the macrophage differentiation process, inhibit the initiation of a specific immune response, modulate cytokine secretion and change the orientation of an immune response. 84,89 Moreover, Wu et al 90 have demonstrated that BEA decreased serum levels of TNF-α and IFN-γ in mice with experimental colitis and suppressed T-cell proliferation and activation, leading to apoptosis of activated T cells and making BEA a novel drug candidate for the treatment of colonic inflammation, such as Crohn's disease.…”

Section: Local Skin Concentrations and Effectsmentioning

confidence: 99%

Human skin permeation of emerging mycotoxins (beauvericin and enniatins)

Taevernier

Veryser

Roche

et al. 2015

J Expo Sci Environ Epidemiol

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Currently, dermal exposure data of cyclic depsipeptide mycotoxins are completely absent. There is a lack of understanding about the local skin and systemic kinetics and effects, despite their widespread skin contact and intrinsic hazard. Therefore, we provide a quantitative characterisation of their dermal kinetics. The emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) were used as model compounds and their transdermal kinetics were quantitatively evaluated, using intact and damaged human skin in an in vitro Franz diffusion cell set-up and ultra high-performance liquid chromatography (UHPLC)-MS analytics. We demonstrated that all investigated mycotoxins are able to penetrate through the skin. ENN B showed the highest permeation (kp,v=9.44 × 10(-6) cm/h), whereas BEA showed the lowest (kp,v=2.35 × 10(-6) cm/h) and the other ENNs ranging in between. Combining these values with experimentally determined solubility data, Jmax values ranging from 0.02 to 0.35 μg/(cm(2) h) for intact skin and from 0.07 to 1.11 μg/(cm(2) h) for damaged skin were obtained. These were used to determine the daily dermal exposure (DDE) in a worst-case scenario. On the other hand, DDE's for a typical occupational scenario were calculated based on real-life mycotoxin concentrations for the industrial exposure of food-related workers. In the latter case, for contact with intact human skin, DDE's up to 0.0870 ng/(kg BW × day) for ENN A were calculated, whereas for impaired skin barrier this can even rise up to 0.3209 ng/(kg BW × day) for ENN B1. This knowledge is needed for the risk assessment after skin exposure of contaminated food, feed, indoor surfaces and airborne particles with mycotoxins.

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“…Several in vitro studies have confirmed cytotoxicity of both compounds in the micromolar range [21,22,23,24,25,26]. These report that enniatin- and beauvericin-induced cell death is primarily based on apoptosis induction via the mitochondrial pathway [22,27,28] or necrosis-induction via lysosomal damage [29,30,31]. Contrasting reports have been made regarding enniatin- and beauvericin-induced oxidative stress [32,33,34].…”

Section: Introductionmentioning

confidence: 99%

Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2)

Springler

Vrubel²,

Mayer³

et al. 2016

Toxins

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The human, animal and plant pathogen Fusarium, which contaminates agricultural commodities worldwide, produces numerous secondary metabolites. An example is the thoroughly-investigated deoxynivalenol (DON), which severely impairs gastrointestinal barrier integrity. However, to date, the toxicological profile of other Fusarium-derived metabolites, such as enniatins, beauvericin, moniliformin, apicidin, aurofusarin, rubrofusarin, equisetin and bikaverin, are poorly characterized. Thus we examined their effects—as metabolites alone and as metabolites in combination with DON—on the intestinal barrier function of differentiated intestinal porcine epithelial cells (IPEC-J2) over 72 h. Transepithelial electrical resistance (TEER) was measured at 24-h intervals, followed by evaluation of cell viability using neutral red (NR) assay. Enniatins A, A1, B and B1, apicidin, aurofusarin and beauvericin significantly reduced TEER. Moniliformin, equisetin, bikaverin and rubrofusarin had no effect on TEER. In the case of apicidin, aurofusarin and beauvericin, TEER reductions were further substantiated by the addition of otherwise no-effect DON concentrations. In all cases, viability was unaffected, confirming that TEER reductions were not due to compromised viability. Considering the prevalence of mycotoxin contamination and the diseases associated with intestinal barrier disruption, consumption of contaminated food or feed may have substantial health implications.

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Enniatin B-induced cell death and inflammatory responses in RAW 267.4 murine macrophages

Cited by 61 publications

References 58 publications

An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays

An investigation of the endocrine disrupting potential of enniatin B using in vitro bioassays

Human skin permeation of emerging mycotoxins (beauvericin and enniatins)

Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2)

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