T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms.
- MeSH
- apoptóza MeSH
- autofagie MeSH
- biologické markery MeSH
- hypoxie buňky MeSH
- lidé MeSH
- signální transdukce MeSH
- T-2 toxin analogy a deriváty metabolismus toxicita MeSH
- vystavení vlivu životního prostředí analýza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The aim of this study was to assess the effects of T-2 toxin-contaminated feed (at concentrations of 1.0 and 1.8 mg/kg) on the rainbow trout immune system by studying non-specific cellular and humoral immune responses and its effect on red and white blood cells. Consumption of T-2 toxin at both concentrations resulted in significantly increased erythrocyte counts and a decrease in mean corpuscular volume. While a significant decrease in mean corpuscular haemoglobin was observed at both experimental concentrations, the decrease in plasma haemoglobin was only significant at the higher T-2 toxin concentration. Higher T-2 toxin concentrations resulted in a significant increase in leukocyte and lymphocyte count, while absolute phagocyte count and counts of less mature neutrophil granulocyte forms remained unchanged at both concentrations. Non-specific humoral immunity (bactericidal activity measured as complement activation) decreased significantly in both experimental groups when compared with the control. The results of this study show that T-2 toxin in feed at a concentration range of 1.0-1.8 mg/kg influences the immunological defence mechanisms of rainbow trout.Trial registration number, MSMT-3876/2014-14; date of registration, 31/1/2014.
- MeSH
- Fusarium chemie metabolismus MeSH
- hemoglobiny metabolismus MeSH
- humorální imunita účinky léků MeSH
- kontaminace potravin analýza MeSH
- krmivo pro zvířata analýza MeSH
- Oncorhynchus mykiss krev imunologie metabolismus mikrobiologie MeSH
- počet erytrocytů MeSH
- počet leukocytů MeSH
- T-2 toxin analýza metabolismus toxicita MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
T-2 toxin, a trichothecene mycotoxin, is a common contaminant in food and animal feed, and is also present in processed cereal products. The most common route of T-2 toxin exposure in humans is through dietary ingestion. The cytotoxic effects of T-2 toxin include modifications to feeding behavior, nervous disorders, cardiovascular alterations, immunosuppression, and hemostatic derangements. However, to date, effects on the central nervous system (CNS) have rarely been reported. In the present study, female Wistar rat were given a single dose of T-2 toxin at 2 mg/kg b.w. and were sacrificed at one, three, and seven days post-exposure. Histopathological analysis and transmission electron microscope (TEM) observations were used to investigate injury to the brain and pituitary gland. Damage to the brain and pituitary at the molecular level was detected by real time-polymerase chain reaction (RT-PCR), western blot, and immunohistochemical assays. Liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) was used to investigate T-2 concentration in the brain. The results showed that pathological lesions were obvious in the brain at three days post-exposure; lesions in the pituitary were not observed until seven days post-exposure. Autophagy in the brain and apoptosis in the pituitary suggest that T-2 toxin may induce different acute reactions in different tissues. Importantly, low concentrations of T-2 toxin in the brain were observed in only one rat. Responsible for the above mentioned, we hypothesize that brain damage caused by this toxin may be due to the ability of the toxin to directly cross the blood-brain barrier (BBB). Therefore, given its widespread pollution in food, we should pay more attention to the neurotoxic effects of the T-2 toxin, which may have widespread implications for human health.
- MeSH
- apoptóza účinky léků MeSH
- autofagie účinky léků MeSH
- časové faktory MeSH
- chování zvířat účinky léků MeSH
- chromatografie kapalinová MeSH
- hematoencefalická bariéra metabolismus MeSH
- hodnocení rizik MeSH
- hypofýza účinky léků metabolismus ultrastruktura MeSH
- imunohistochemie MeSH
- kapilární permeabilita MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- mozek účinky léků metabolismus ultrastruktura MeSH
- neurotoxické syndromy etiologie metabolismus patologie psychologie MeSH
- potkani Wistar MeSH
- regulace genové exprese MeSH
- T-2 toxin metabolismus toxicita MeSH
- tandemová hmotnostní spektrometrie MeSH
- transmisní elektronová mikroskopie MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Pro organismus člověka představují mykotoxiny významné zdravotní riziko, které je potřeba řídit, tj. minimalizovat jeho dopady na lidské zdraví. Biologické účinky mykotoxinů jsou podmíněné jejich rozdílnou chemickou strukturou. K významným patří např. také skupina tzv. epoxytrichotecenů, např. DON, DAS (diacetoxyscirpenol), nivalenol, T-2 toxin, fusarenony, satratoxiny, roridiny, verukariny aj., kterých bylo popsáno více než 170. Rozhodujícími faktory toxického účinku mykotoxinů obecně, tedy i trichotecenů, jsou dávka a délka doby jejich působení (velikost expozice), individuální citlivost, věk, pohlaví, zdravotní stav a stav výživy, vitaminová deficience, abúzus alkoholu a infekční onemocnění. Kombinace dvou či více současně se vyskytujících tzv. „emerging“ (vznikajících) mykotoxinů či tzv. „maskovaných“ mykotoxinů v surovinách i potravinách může v důsledku synergického spolupůsobení (při uvažované dietární expozici) působit mnohem toxičtěji. Za toxikologicky významné trichoteceny jsou považovány např. deoxynivalenol (DON) a T-2 toxin (jehož limit v potravinách v EU je stále diskutovaným a nedořešeným problémem), z dalších by si zasloužil regulaci také např. hematotoxický nivalenol aj. Zcela nepochybně by se v této skupině našla celá řada dalších, zasluhujících pozornost. Pro svoji toxicitu a možné zneužití jsou (epoxy)trichoteceny v ČR v působnosti zákona č. 281/2002 Sb. a jeho prováděcí vyhlášky č. 474/2002 Sb., o některých opatřeních souvisejících se zákazem bakteriologických (biologických) a toxinových zbraní. Záměrem této práce je proto sledování některých toxických účinků vybraných epoxytrichotecenů.
In the human organism, mycotoxins present a considerable risk, which must be controlled, i.e. its impact on the human health should be minimized. Biological effects of mycotoxins are associated with their different chemical structures. Important mycotoxins also include a group of so called epoxytrichothecenes, as for example DON, DAS (diacetoxyscirpenol), nivalenol, T-2 toxin, fusarenons, satratoxins, roridins, verrucarins, etc. which have been described in a number exceeding 170. The decisive factors determining toxic effects of mycotoxins in general, and thus also of trichothecenes, are their dose and time period of their action (the magnitude of the exposure), individual sensitivity, age, gender, condition of health and nutrition, vitamin deficiency, alcohol abuse and infectious diseases. Combinations of two or more so called “emerging” or “masked” mycotoxins concomitantly occurring in foodstuffs and/or raw materials can, as a result of their synergism (at a dietary exposure considered), induce much higher toxic effects. Toxicologically important mycotoxins are trichothecenes as for example deoxynivalenol (DON) and T-2 toxin (its limit concentrations being a still discussed and yet not solved problem in the EU); regulation should also be considered for haematotoxic nivalenol, etc. Appropriate attention should also be undoubtedly paid to a number of further species. Due to their toxicity and possible abuse, in the Czech Republic, (epoxy)trichothecenes are subjected to the force of Law No. 281/2002 Sb and its executing Regulation No. 474/2002 Sb. “On some provisions associated with the prohibition of bacteriological (biological) and toxin weapons”. The purpose of the work presented here is thus monitoring of certain toxic effects of selected epoxytrichothecenes.
Among the naturally-occurring trichothecenes found in food and feed, T-2 toxin is the most potent and toxic mycotoxin. After ingestion of T-2 toxin into the organism, it is processed and eliminated. Some metabolites of this trichothecene are equally toxic or slightly more toxic than T-2 itself, and therefore, the metabolic fate of T-2 toxin has been of great concern. The main reactions in trichothecene metabolism are hydrolysis, hydroxylation and deep oxidation. Typical metabolites of T-2 toxin in an organism are HT-2 toxin, T-2-triol, T-2-tetraol, 3'-hydroxy-T-2, and 3'-hydroxy-HT-2 toxin. There are significant differences in the metabolic pathways of T-2 toxin between ruminants and non-ruminants. Ruminants have been more resistant to the adverse effects of T-2 toxin due to microbial degradation within rumen microorganisms. Some plant species are resistant to T-2 toxin, while others are capable of its intake and metabolisation.
- MeSH
- bachor metabolismus mikrobiologie MeSH
- Bacteria metabolismus MeSH
- biotransformace MeSH
- financování organizované MeSH
- houby metabolismus MeSH
- hydrolýza MeSH
- hydroxylace MeSH
- oxidace-redukce MeSH
- půdní mikrobiologie MeSH
- rostliny metabolismus MeSH
- sladká voda mikrobiologie MeSH
- T-2 toxin metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- přehledy MeSH
