Cytotoxicity and apoptosis induced by mixed mycotoxins (T-2 and HT-2 toxin) on primary hepatocytes of broilers in vitro

Yang, Lingchen; Tu, Di; Zhao, Zhiyong; Cui, Jun

doi:10.1016/j.toxicon.2017.01.001

Cited by 40 publications

(26 citation statements)

References 38 publications

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“…The mechanism involved in T-2 and DON toxicity is generally via oxidative stress-mediated deoxyribonucleic acid (DNA) damage and apoptosis (Wu et al, 2014 ). Furthermore, T-2 and DON are well-known inhibitors of protein synthesis resulting from the binding of peptidyl-transferase, which is located in the 60s ribosomal subunit (Yang et al, 2017 ).…”

Section: Gastrointestinal Tractmentioning

confidence: 99%

Mycotoxin: Its Impact on Gut Health and Microbiota

Liew

Sabran

2018

Front. Cell. Infect. Microbiol.

317

195

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The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and mycotoxicosis.

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Section: Gastrointestinal Tractmentioning

confidence: 99%

Mycotoxin: Its Impact on Gut Health and Microbiota

Liew

Sabran

2018

Front. Cell. Infect. Microbiol.

317

195

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“…Previous studies have shown that T-2 toxin injection can strongly induce cell apoptosis in different tissues, such as thymus, spleen and liver, particularly in the liver [6]. Yang et al incubated primary chicken hepatocytes with T-2 toxin for 24 h and found that the cell activity was significantly reduced and apoptosis gradually increased in a dose-dependent manner [9], which was similar to our finding that hepatocyte apoptosis gradually increased with the increasing dosage of T-2 toxin.…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have shown that T-2 toxin induces apoptotic cell death in hematopoietic tissue [5], spleen, liver [6], skin and intestinal crypt in mice [7]. In chickens, apoptosis induced by T-2 toxin was detected in the thymus, bursa of Fabricius and primary hepatocytes [8,9]. Previous studies have demonstrated a crosstalk between autophagy and apoptosis, as apoptosis increases when the autophagic pathway is completely inhibited [10].…”

Section: Introductionmentioning

confidence: 99%

T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

Yin

Han

Chen

et al. 2020

Toxins

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T-2 toxin is type A trichothecenes mycotoxin, which produced by fusarium species in cereal grains. T-2 toxin has been shown to induce a series of toxic effects on the health of human and animal, such as immunosuppression and carcinogenesis. Previous study has proven that T-2 toxin caused hepatotoxicity in chicken, but the regulatory mechanism is unclear. In the present study, we assessed the toxicological effect of T-2 toxin on apoptosis and autophagy in hepatocytes. The total of 120 1-day-old healthy broilers were allocated randomly into four groups and reared for 21 day with complete feed containing 0 mg/kg, 0.5 mg/kg, 1 mg/kg or 2 mg/kg T-2 toxin, respectively. The results showed that the apoptosis rate and pathological changes degree hepatocytes were aggravated with the increase of T-2 toxin. At the molecular mechanism level, T-2 toxin induced mitochondria-mediated apoptosis by producing reactive oxygen species, promoting cytochrome c translocation between the mitochondria and cytoplasm, and thus promoting apoptosomes formation. Meanwhile, the expression of the autophagy-related protein, ATG5, ATG7 and Beclin-1, and the LC3-II/LC3-I ratio were increased, while p62 was downregulated, suggesting T-2 toxin caused autophagy in hepatocytes. Further experiments demonstrated that the PI3K/AKT/mTOR signal may be participated in autophagy induced by T-2 toxin in chicken hepatocytes. These data suggest a possible underlying molecular mechanism for T-2 toxin that induces apoptosis and autophagy in chicken hepatocytes

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“…Cell viability was assessed through MTT [3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide] assay [6,7]. Dilute cells in 96-well microplates to a density of 5×10 4 cells/well including 200 µL mixtures.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Triterpenes From Docynia Indica Fruits and Their Cytotoxic Activity

Duy¹

2018

JST

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Five triterpenes were isolated from the ethyl acetate fraction of methanolic extract of Docynia indica fruits. Their structures were determined to be pomolic acid (1), maslinic acid (2), ursolic acid (3), 23-hydroxy ursolic acid (4) and euscaphic acid (5) by comparison of physicochemical, NMR and mass spectral data with those reported in the literature. All triterpenes (1 – 5) were isolated for the first time from Docynia indica. Compounds 1 – 5 were evaluated for their cytotoxic activity using MTT assay, of which 23-hydroxy ursolic acid (3) and ursolic acid (4) showed cytotoxic activities against HeLa and Hep-G2 cancer cell lines.

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Cytotoxicity and apoptosis induced by mixed mycotoxins (T-2 and HT-2 toxin) on primary hepatocytes of broilers in vitro

Cited by 40 publications

References 38 publications

Mycotoxin: Its Impact on Gut Health and Microbiota

Mycotoxin: Its Impact on Gut Health and Microbiota

T-2 Toxin Induces Oxidative Stress, Apoptosis and Cytoprotective Autophagy in Chicken Hepatocytes

Triterpenes From Docynia Indica Fruits and Their Cytotoxic Activity

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