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Statements

Subject Item
n2:RIV%2F62690094%3A18470%2F14%3A50002387%21RIV15-MSM-18470___
rdf:type
skos:Concept n12:Vysledek
dcterms:description
Trichothecenes are a large family of structurally related toxins mainly produced by Fusarium genus. Among the trichothecenes, T-2 toxin and deoxynivalenol (DON) cause the most concern due to their wide distribution and highly toxic nature. Trichothecenes are known for their inhibitory effect on eukaryotic protein synthesis, and oxidative stress is one of their most important underlying toxic mechanisms. They are able to generate free radicals, including reactive oxygen species, which induce lipid peroxidation leading to changes in membrane integrity, cellular redox signaling, and in the antioxidant status of the cells. The mitogen-activated protein kinases signaling pathway is induced by oxidative stress, which also induces caspase-mediated cellular apoptosis pathways. Several new metabolites and novel metabolic pathways of T-2 toxin have been discovered very recently. In human cell lines, HT-2 and neosolaniol (NEO) are the major metabolites of T-2 toxin. Hydroxylation on C-7 and C-9 are two novel metabolic pathways of T-2 toxin in rats. The metabolizing enzymes CYP3A22, CYP3A29, and CYP3A46 in pigs, as well as the enzymes CYP1A5 and CYP3A37 in chickens, are able to catalyze T-2 toxin and HT-2 toxin to form the C-3'-OH metabolites. Similarly to carboxylesterase, CYP3A29 possesses the hydrolytic ability in pigs to convert T-2 toxin to NEO. T-2 toxin is able to down- or upregulate cytochrome P-450 enzymes in different species. The metabolism of DON in humans is region-dependent. Free DON and DON-glucuronide are considered to be the biomarkers for humans. The masked mycotoxin DON-3-beta-D-glucoside can be hydrolyzed to free DON in the body. This review will provide useful information on the progress of oxidative stress as well as on the metabolism and the metabolizing enzymes of T-2 toxin and DON. Moreover, the literature will throw light on the blind spots of metabolism and toxicological studies in trichothecenes that have to be explored in the future. Trichothecenes are a large family of structurally related toxins mainly produced by Fusarium genus. Among the trichothecenes, T-2 toxin and deoxynivalenol (DON) cause the most concern due to their wide distribution and highly toxic nature. Trichothecenes are known for their inhibitory effect on eukaryotic protein synthesis, and oxidative stress is one of their most important underlying toxic mechanisms. They are able to generate free radicals, including reactive oxygen species, which induce lipid peroxidation leading to changes in membrane integrity, cellular redox signaling, and in the antioxidant status of the cells. The mitogen-activated protein kinases signaling pathway is induced by oxidative stress, which also induces caspase-mediated cellular apoptosis pathways. Several new metabolites and novel metabolic pathways of T-2 toxin have been discovered very recently. In human cell lines, HT-2 and neosolaniol (NEO) are the major metabolites of T-2 toxin. Hydroxylation on C-7 and C-9 are two novel metabolic pathways of T-2 toxin in rats. The metabolizing enzymes CYP3A22, CYP3A29, and CYP3A46 in pigs, as well as the enzymes CYP1A5 and CYP3A37 in chickens, are able to catalyze T-2 toxin and HT-2 toxin to form the C-3'-OH metabolites. Similarly to carboxylesterase, CYP3A29 possesses the hydrolytic ability in pigs to convert T-2 toxin to NEO. T-2 toxin is able to down- or upregulate cytochrome P-450 enzymes in different species. The metabolism of DON in humans is region-dependent. Free DON and DON-glucuronide are considered to be the biomarkers for humans. The masked mycotoxin DON-3-beta-D-glucoside can be hydrolyzed to free DON in the body. This review will provide useful information on the progress of oxidative stress as well as on the metabolism and the metabolizing enzymes of T-2 toxin and DON. Moreover, the literature will throw light on the blind spots of metabolism and toxicological studies in trichothecenes that have to be explored in the future.
dcterms:title
Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update
skos:prefLabel
Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update Oxidative stress-mediated cytotoxicity and metabolism of T-2 toxin and deoxynivalenol in animals and humans: an update
skos:notation
RIV/62690094:18470/14:50002387!RIV15-MSM-18470___
n3:aktivita
n17:I
n3:aktivity
I
n3:cisloPeriodika
7
n3:dodaniDat
n10:2015
n3:domaciTvurceVysledku
n18:3289133
n3:druhVysledku
n4:J
n3:duvernostUdaju
n8:S
n3:entitaPredkladatele
n16:predkladatel
n3:idSjednocenehoVysledku
35540
n3:idVysledku
RIV/62690094:18470/14:50002387
n3:jazykVysledku
n14:eng
n3:klicovaSlova
Metabolizing enzymes; Metabolism; ROS; Oxidative stress; Deoxynivalenol (DON); T-2 toxin
n3:klicoveSlovo
n6:ROS n6:Deoxynivalenol%20%28DON%29 n6:Oxidative%20stress n6:T-2%20toxin n6:Metabolism n6:Metabolizing%20enzymes
n3:kodStatuVydavatele
DE - Spolková republika Německo
n3:kontrolniKodProRIV
[EF5F9F3A6993]
n3:nazevZdroje
Archives of toxicology
n3:obor
n15:FP
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
9
n3:rokUplatneniVysledku
n10:2014
n3:svazekPeriodika
88
n3:tvurceVysledku
Wang, Xu Yang, Wei Nüssler, Andreas K Zhang, Xiu-Juan Yuan, Zong-Hui Xiong, Ling-Yun Wu, Qinghua Kuča, Kamil Dohnal, Vlastimil
n3:wos
000338283400003
s:issn
0340-5761
s:numberOfPages
18
n13:doi
10.1007/s00204-014-1280-0
n9:organizacniJednotka
18470