Cytotoxic and apoptotic effect of mycotoxins in human small intestinal cells
          
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Nielsen, Tina Skau; Sørensen, Izel Fourie; Sørensen, Jens Laurids; Søndergaard, Teis Esben; Purup, Stig

doi:10.2527/jas.2015-9739

Cited by 7 publications

(4 citation statements)

References 9 publications

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“…These results are in accordance with observations of Fernández-Blanco et al [55] studying the cytotoxicity of AME (0-100 µM) in Caco-2 cells. The same result for MPA was reported by Nielsen et al [56] in human small intestinal cells, where no IC 50 values were achieved up to 156 nM concentration. Previous studies showed a statistically significant decrease in viability of cells treated at concentrations of BEA (3 µM), DON (1 µM), ZEA (25 µM), ENN-A (1 µM), A1 (1 µM), B (2 µM), B1 (2 µM), AOH (50 µM), and AME (25 µM) [14,19,57,58].…”

Section: In Silico Prediction Of Physicochemical Pharmacological Andsupporting

confidence: 88%

“…These authors assessed the cytotoxicity of 14 mycotoxins in Chinese hamster lung fibroblast (V79 cells) and characterized T-2 as the most potent cytotoxic agent, followed by HT-2 and the other toxins tested. Similarly, previous studies also reported the IC 50 values for T-2 in the range of 3-500 nM in various mammalian cells [21,56,59,60]. The chemical analysis showed the following concentrations of acutely toxic mycotoxins expected to be in human blood after exposure to the recommended daily dose of milk thistle-based dietary supplement: 6.2 nM of T-2, 5.0 nM of HT-2, and 0.04 nM of DAS.…”

Section: In Silico Prediction Of Physicochemical Pharmacological Andsupporting

confidence: 70%

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In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

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Section: In Silico Prediction Of Physicochemical Pharmacological Andsupporting

confidence: 88%

Section: In Silico Prediction Of Physicochemical Pharmacological Andsupporting

confidence: 70%

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Tran

Viktorová

Augustynkova

et al. 2020

Toxins

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“…The toxic effects of NIV and T-2/HT-2 include the inhibition of protein synthesis, reduction of the immune defence and an effect on growth in exposed animals (Torp & Langseth, 1999;Poapolathep et al, 2002;Nielsen et al, 2016). During oat processing (dehulling, milling and flaking), some removal of these toxins occurs, but this leads to an increase in toxin in the resulting by-products that are often used as animal fodder (Pettersson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Influence of temperature, humidity duration and growth stage on the infection and mycotoxin production by Fusarium langsethiae and Fusarium poae in oats

et al. 2018

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High occurrence of Fusarium poae (FP) and Fusarium langsethiae (FL) and their mycotoxins nivalenol (NIV) and T‐2/HT‐2 have been observed in Swiss oats. Early prediction of mycotoxin levels is important for farmers and the cereal industry to minimize the risk of contaminated food and feed. Therefore, climate chamber experiments were conducted to investigate the influence of different temperatures (10, 15, 20 °C) and durations (4, 8, 12 h) at 99% relative humidity (RH) on the infection of oats with FP and FL. In addition, to discover the most susceptible period of oats, artificial FL inoculations were conducted at different growth stages. Field experiments were performed to observe the dispersal of these fungal species within the field and to investigate the weather conditions that influence the dispersal. The climate chamber experiments revealed higher contamination with NIV and T‐2/HT‐2 in the 10 °C treatments and with a prolonged humidity duration of 12 h 99% RH. Inoculations of oat plants at early (DC 61) and mid (DC 65) anthesis, led to higher FL infection and T‐2/HT‐2 accumulation in the grains compared with treatments at earlier growth stages, which might be due to an increased susceptibility during anthesis. No indication for spore dispersal was observed in the field experiments. The results obtained, together with the cropping factors that influence infection and mycotoxin production, could be used as a first step in developing forecasting models to predict the contamination of oats with the mycotoxins NIV and T‐2/HT‐2.

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“…According to previous research, the individual cytotoxic sensitivities of DON and T-2 toxin depend on the species, cell type and exposure time (Ficheux et al, 2012, Lei et al, 2017, Nielsen, Sorensen, Sorensen, Sondergaard, & Purup, 2016, Ruiz, Franzova, et al, 2011, Ruiz, Macakova, et al, 2011, Thuvander et al, 1999 (Supporting information Table S1). However, the toxicity sensitivity of chondrocytes among species to DON or T-2 toxin is limited.…”

Section: Quantifying Interactions Between Deoxynivalenol and T-2 Tomentioning

confidence: 92%

Individual and combined toxicity of T‐2 toxin and deoxynivalenol on human C‐28/I2 and rat primary chondrocytes

Lin

Shao

et al. 2018

J of Applied Toxicology

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Deoxynivalenol (DON) and T‐2 toxin are prevalent mycotoxin contaminants in the food and feed stuffs worldwide, with non‐negligible co‐contamination and co‐exposure conditions. Meanwhile, they are considerable risk factors for Kashin‐Beck disease, a chronic endemic osteochondropathy. The aim of this study was to investigate the individual and combined cytotoxicity of DON and T‐2 toxin on proliferating human C‐28/I2 and newborn rat primary costal chondrocytes by MTT assay. Four molar concentration combination ratios of DON and T‐2 toxin were used, 1:1 for R1 mixture, 10:1 for R10, 100:1 for R100 and 1000:1 for R1000. The toxicological interactions were quantified by the MixLow method. DON, T‐2 toxin, and their mixtures all showed a clear dose‐dependent toxicity for chondrocytes. The cytotoxicity of T‐2 toxin was 285‐fold higher than DON was in human chondrocytes, and 22‐fold higher in the rat chondrocytes. The combination of DON and T‐2 toxin was significantly synergistic at middle and high level concentrations of R10 mixtures in rat chondrocytes, but significantly antagonistic at the low concentrations of R100 mixtures in both cells and at the middle concentrations of R1000 mixtures in rat chondrocytes. These results indicated that the combined toxicity was influenced by the cell sensitivity for toxins, the difference between the combination ratio and equitoxic ratio, the concentrations and other factors.

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Cytotoxic and apoptotic effect of mycotoxins in human small intestinal cells 1

Cited by 7 publications

References 9 publications

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Influence of temperature, humidity duration and growth stage on the infection and mycotoxin production by Fusarium langsethiae and Fusarium poae in oats

Individual and combined toxicity of T‐2 toxin and deoxynivalenol on human C‐28/I2 and rat primary chondrocytes

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