Mechanisms of beauvericin toxicity and antioxidant cellular defense

Mallebrera, Beatriz; Juan-García, Ana; Font, Guillermina; Ruiz, María-José

doi:10.1016/j.toxlet.2016.01.013

Cited by 60 publications

(34 citation statements)

References 39 publications

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“…*P < .05, **P < .01. CG, calycosin-7-O-β-D-glucoside together, initially convert superoxide radicals to H 2 O 2 and then to molecular oxygen and water (Goc, Szaroma, Kapusta, & Dziubek, 2017;Mallebrera, Juan-Garcia, Font, & Ruiz, 2016). In the present study, CG increased the enzyme activities of SOD and CAT compared with the control.…”

Section: Discussionsupporting

confidence: 59%

Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

Zhang

Xue

Yang

et al. 2018

J of Applied Toxicology

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Calycosin-7-O-β-d-glucoside (CG) is an important active isoflavone compound in Radix Astragali that has many bioactivities. However, the toxicological effects and related toxicological mechanism of CG have been rarely documented. The purpose of the present study was to evaluate the toxicity effects of CG on the model organism Caenorhabditis elegans. Some characteristics of the nematode, including lifespan, movement behavior and reproductive capacity, were used to detect the toxic effects of CG on C. elegans. The results showed that CG could shorten the lifespan of C. elegans by up to 25.3% and severely damage the movement of N2 larvae compared with the control group. Moreover, CG could prolong the generation times and reduce the brood sizes. Furthermore, CG promoted the formation of reactive oxygen species (ROS), which caused oxidative stress, increased the mRNA expression of sod-1, sod-2, sod-3, sod-5, ctl-1, ctl-2 and ctl-3, and induced the antioxidant enzymes activities of superoxide dismutase and catalase to scavenge free radicals. However, antioxidant treatment experiments showed that Trolox could reduce the level of ROS caused by CG to the normal state of the control. These results suggested that the generation and elimination of ROS could not restore normal homeostasis in C. elegans treated by CG. These findings indicated that the activation of oxidative damage is one of the most important toxic mechanisms of CG in C. elegans.

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Section: Discussionsupporting

confidence: 59%

Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

Zhang

Xue

Yang

et al. 2018

J of Applied Toxicology

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“…A genotoxic effect was also demonstrated, by MN and Comet assay in porcine kidney epithelial cells PK15 and in human leukocytes with a different sensitivity (Klaric et al 2008(Klaric et al , 2010. CHO-K1 cells treated with different concentrations of BEA showed an increase of DNA damage as assessed by Comet assay, which was not dose dependent (Mallebrera et al 2016). Possible mechanisms of BEA DNA damage induction have been investigated in a study (Dornetshuber et al 2009) and the capacity of BEA to intercalate into the double helix was demonstrated but only at cytotoxic concentrations; an inhibition of topoisomerases activity was also shown at high concentrations.…”

Section: Toxicity Of Beauvericin and Enniatin Bmentioning

confidence: 83%

In vivo toxicity and genotoxicity of beauvericin and enniatins. Combined approach to study in vivo toxicity and genotoxicity of mycotoxins beauvericin (BEA) and enniatin B (ENNB)

Maranghi

Tassinari

Narciso

et al. 2018

EFS3

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Beauvericin (BEA) and Enniatins (ENN) are mycotoxins produced by Fusarium fungi detected in food and feed; there are insufficient data to establish their reference values. To evaluate BEA and ENN oral toxicity, an integrated approach was applied. Among ENN, Enniatin B (ENNB) was selected as test substance. The approach is composed by: i) in vitro and acute in vivo genotoxicity tests; ii) a repeated‐dose oral toxicity study focused on genotoxic, immune, endocrine, nervous endpoints and the reproductive/developmental toxicity screening. For BEA, all the genotoxicity endpoints yielded negative results excluding Comet assay in duodenum and kidney after repeated doses. BEA immunotoxicity was observed in female mice, concentrated in number and functional activity of effector T cells in the spleen. Based on the repeated‐dose BEA study, the No Observed Adverse Effect Level (NOAEL) for female mice is 1 mg/kg b.w. per day (increased thyroid pycnotic nuclei and endometrial hyperplasia). In males, the NOAEL is 0.1 mg/kg b.w. per day (reduced colloid and altered T4 serum levels). Maternal NOAEL is 0.1 mg/kg b.w. per day (increased thymus weight), developmental NOAEL is 10 mg/kg b.w. per day. For ENNB, the results support a genotoxic effect in bone marrow and liver cells after acute treatment, but not after repeated exposure. Immunotoxic ENNB effects were observed in both genders, suggestive of a suppressive/inhibiting activity particularly evident in males. Based on the repeated‐dose ENNB study, the NOAEL for females is 0.18 mg/kg b.w. per day (histomorphometrical effects on thymus, uterus and spleen). In male mice, the NOAEL is 1.8 mg/kg b.w. per day (enterocyte vacuolization in duodenum and increased Reactive Oxygen Species and reduced Glutathione brain levels). The maternal NOAEL is 1.8 mg/kg b.w. per day (decreased white pulp area and increased red/white pulp area ratio in spleen), developmental NOAEL is 18 mg/kg b.w. per day.

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“…The reason is that, after 5 µM BEA exposure, antioxidant defense system activities were stimulated and therefore highly contributed to eliminate cell damage. Moreover, BEA inhibited the proliferation of damaged cells arresting them in G0/G1 phase and thus increased the apoptosis [73].…”

Section: Genotoxicity Of Single Mycotoxinsmentioning

confidence: 99%

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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Mechanisms of beauvericin toxicity and antioxidant cellular defense

Cited by 60 publications

References 39 publications

Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

Multiple biological defects caused by calycosin‐7‐O‐β‐d‐glucoside in the nematode Caenorhabditis elegans are associated with the activation of oxidative damage

In vivo toxicity and genotoxicity of beauvericin and enniatins. Combined approach to study in vivo toxicity and genotoxicity of mycotoxins beauvericin (BEA) and enniatin B (ENNB)

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

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