Intestinal metabolism of T-2 toxin in the pig cecum model

Wu, Qinghua; Engemann, Anna; Cramer, Benedikt; Welsch, Tanja; Zhang, Yuan; Humpf, Hans‐Ulrich

doi:10.1007/s12550-012-0134-y

Cited by 19 publications

(16 citation statements)

References 38 publications

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“…No HT-2 toxin was detectable after incubations with T-2 toxin, while this conversion is well described in literature for various cell types in vitro : primary cells of different human origin like RPTEC (kidney), NHA (astrocytes), NHLF (lung fibroblasts) as well as cell lines derived from human colon carcinoma cells (HT-29) metabolize T-2 toxin rapidly to HT-2 toxin [10], [11]. Metabolism studies mimicking the human gastrointestinal tract found also HT-2 toxin as the main or even sole metabolite after T-2 toxin application [25]. In PBCEC, the lack of metabolizing T-2 toxin could also be partly responsible for the high sensitivity of these cells against T-2 toxin.…”

Section: Resultsmentioning

confidence: 99%

“…Both toxins were chosen since most studies concerning effects on the CNS dealt only with T-2 toxin neglecting its main metabolite HT-2 toxin which was already shown to exhibit similar cytotoxic effects as the parent toxin on various cell types [10]. HT-2 toxin was also formed following T-2 toxin application after short incubation periods in in vitro studies in primary human kidney cells [10], [11] as well as in a model reflecting the metabolism in the human gastrointestinal tract [25] indicating its potential presence in vivo after T-2 toxin ingestion. In this study, the BBB was mimicked by porcine brain capillary endothelial cells (PBCEC) seeded on polycarbonate Transwell® filter inserts [26].…”

Section: Introductionmentioning

confidence: 99%

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Influence of T-2 and HT-2 Toxin on the Blood-Brain Barrier In Vitro: New Experimental Hints for Neurotoxic Effects

et al. 2013

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The trichothecene mycotoxin T-2 toxin is a common contaminant of food and feed and is also present in processed cereal derived products. Cytotoxic effects of T-2 toxin and its main metabolite HT-2 toxin are already well described with apoptosis being a major mechanism of action. However, effects on the central nervous system were until now only reported rarely. In this study we investigated the effects of T-2 and HT-2 toxin on the blood-brain barrier (BBB) in vitro. Besides strong cytotoxic effects on the BBB as determined by the CCK-8 assay, impairment of the barrier function starting at low nanomolar concentrations were observed for T-2 toxin. HT-2 toxin, however, caused barrier disruption at higher concentrations compared to T-2 toxin. Further, the influence on the tight junction protein occludin was studied and permeability of both toxins across the BBB was detected when applied from the apical (blood) or the basolateral (brain) side respectively. These results clearly indicate the ability of both toxins to enter the brain via the BBB.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of T-2 and HT-2 Toxin on the Blood-Brain Barrier In Vitro: New Experimental Hints for Neurotoxic Effects

et al. 2013

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“…Wu et al reported that the T-2 toxin can be rapidly metabolized to HT-2 toxin in microsomes of some animals' tissues and the conversion rates are 80% [6]. The HT-2 toxin has exerted various toxic effects on multiple systems, such as digestive [7], immune [8], and reproductive systems [9]. Previous studies reported that ZEA and T-2 impaired mammalian oocyte quality [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Understanding the Toxin Effects of β-Zearalenol and HT-2 on Bovine Granulosa Cells Using iTRAQ-Based Proteomics

Yang

et al. 2020

Animals

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Zearalenone (ZEA) and T-2 are the most common mycotoxins in grains and can enter the animal and human food-chain and cause many health disorders. To elucidate the toxic response profile, we stimulated bovine granulosa cells (GCs) with β-zearalenol or HT-2. Using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic, 178 and 291 differentially expressed proteins (DEPs, fold change ≥ 1.3 and p-value < 0.05) in β-zearalenol and HT-2 groups were identified, respectively. Among these DEPs, there were 66 common DEPs between β-zearalenol and HT-2 groups. These 66 DEPs were associated with 23 biological processes terms, 14 molecular functions terms, and 19 cellular components terms. Most heat shock proteins (HSPs) were involved in the toxic response. Reactive oxygen species accumulation, the endoplasmic reticulum (ER)-stress related marker molecule (GRP78), and apoptosis were activated. β-zearalenol and HT-2 inhibited oestradiol (E2) production. These results emphasized the important function of HSPs, clarified oxidative stress, and demonstrated the caspase-3 signaling cascade involved in mycotoxin-treated toxic response, along with decreased E2 production. This study offers new insights into the toxicity of β-zearalenol and HT-2 on ovarian granulosa cells.

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“…In humans and animals, the T-2 toxin causes general signs of the so-called shock-like syndrome, accompanied with emesis, lowered weight gain, lethargy, bloody diarrhea, gastric and intestinal disorders, haemorrhaging, immunosuppression, cardiomyopathy, and finally death [ 13 , 14 , 15 , 16 , 17 , 18 ]. Furthermore, similarly to acute radiation syndrome [ 19 , 20 , 21 ], inflammatory reaction, caused by the T-2 toxin, is a consequence of phospholipase A2 activation, successive prostaglandins, and reactive oxygen species (ROS) production [ 15 , 22 , 23 ]. Intensive accumulation of ROS may lead to DNA damage, protein oxidation, and lipid peroxidation [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

“…As mentioned earlier, these intensive gastric injuries are not only thanks to a local toxic effect [ 9 , 20 ], but to biliary excretion and enterohepatic recirculation of the T-2 and HT-2 toxins as well, [ 15 , 21 ] causing generalized toxic effects [ 34 ]. By providing the previously demonstrated mechanism of gastric toxicity induced by the T-2 toxin, an approach that supports the use of adsorbents seems to be rational.…”

Section: Introductionmentioning

confidence: 99%

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

Jacević

Dumanović

Lazarević

et al. 2020

Toxins

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In this paper, the potential antidote efficacy of commercially available formulations of various feed additives such as Minazel-Plus®, Mycosorb®, and Mycofix® was considered by recording their incidence on general health, body weight, and food and water intake, as well as through histopathology and semiquantitative analysis of gastric alterations in Wistar rats treated with the T-2 toxin in a single-dose regimen of 1.67 mg/kg p.o. (1 LD50) for 4 weeks. As an organic adsorbent, Mycosorb® successfully antagonized acute lethal incidence of the T-2 toxin (protective index (PI) = 2.25; p < 0.05 vs. T-2 toxin), and had adverse effects on body weight gain as well as food and water intake during the research (p < 0.001). However, the protective efficacy of the other two food additives was significantly lower (p < 0.05). Treatment with Mycosorb® significantly reduced the severity of gastric damage, which was not the case when the other two adsorbents were used. Our results suggest that Mycosorb® is a much better adsorbent for preventing the adverse impact of the T-2 toxin as well as its toxic metabolites compared with Minazel-plus® or Mycofix-plus®, and it almost completely suppresses its acute toxic effects and cytotoxic potential on the gastric epithelial, glandular, and vascular endothelial cells.

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Intestinal metabolism of T-2 toxin in the pig cecum model

Cited by 19 publications

References 38 publications

Influence of T-2 and HT-2 Toxin on the Blood-Brain Barrier In Vitro: New Experimental Hints for Neurotoxic Effects

Influence of T-2 and HT-2 Toxin on the Blood-Brain Barrier In Vitro: New Experimental Hints for Neurotoxic Effects

Understanding the Toxin Effects of β-Zearalenol and HT-2 on Bovine Granulosa Cells Using iTRAQ-Based Proteomics

Antidotal Potency of the Novel, Structurally Different Adsorbents in Rats Acutely Intoxicated with the T-2 Toxin

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