T-2 toxin immunotoxicity on human B and T lymphoid cell lines

Minervini, Fabrizio; Fornelli, Francesca; Lucivero, Giacomo; Romano, Ciro; Visconti, Angelo

doi:10.1016/j.tox.2005.01.007

Cited by 63 publications

(48 citation statements)

References 24 publications

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“…T-2 is the most toxic trichothecene which inhibits protein synthesis following decreased DNA and RNA synthesis (Gutleb et al 2002). T-2 affects cell division mechanisms in the gastric mucosa, skin, lymphoid and erythroid cells, and it can also decrease antibody, immunoglobulin and cytokine levels ( Niyo et al 1988, Minervini et al 2005. T-2 is believed to be the main cause of alimentary toxic aleukia (ATA) in humans (Canady et al 2001).…”

Section: Discussionmentioning

confidence: 99%

The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches

Obremski

Podlasz²,

Żmigrodzka³

et al. 2013

Polish Journal of Veterinary Sciences

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The immune system is one of the main toxicity targets of the T-2 toxin. In view of scant research data demonstrating the effect of T-2 on cellular and humoral responses in gut-associated lymphoid tissue (GALT), this study set out to investigate the effects of chronic exposure to low doses of the T-2 toxin (200 μg T-2 toxin kg -1 feed) on percentages of CD4 + and CD8 + T lymphocytes, CD4 + /CD8 + double-positive T lymphocytes, CD21 + B cells, and IL-2, IFN-γ, IL-4 and IL-10 mRNA expression levels in porcine ileal Peyer's patches. The investigated material comprised ileum sections sampled from piglets (aged 8-10 weeks, body weight of 15-18 kg) on days 14, 28 and 42 of the experiment.After 42 days of exposure to T-2, a significant drop in the quantity of the IL-10 product was observed (R=0.94; S.E. 0.49-0.79; p<0.001). A gradual decrease in the amount of IL-4 and IFN-γ cytokine transcripts was found throughout the experiment, but the reported trend was not significant. On experimental days 14 and 42, a significant increase in the percentage of CD8 + T lymphocytes was observed in comparison with the control (p=0.04 and p=0.05, respectively), whereas on day 28, a significant decrease in the percentage of the above subpopulation was noted (p=0.00). The percentage of CD21 + B cells in the experimental group decreased steadily in comparison with the control, and the observed drop was significant on days 28 and 42 (p=0.06 and p=0.00, respectively). On days 14 and 28, the percentages of CD4 + and CD8 + T lymphocytes were lower in the experimental animals than in the control group, and the drop reported on day 28 was statistically significant (p=0.03).

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Section: Discussionmentioning

confidence: 99%

The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches

Obremski

Podlasz²,

Żmigrodzka³

et al. 2013

Polish Journal of Veterinary Sciences

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“…T-2 toxin has been found to contaminate human foods, animal foods and agricultural products, which has been reported in many parts of the world (WHO, 1990). Although it is known that T-2 toxin induces lipid peroxidation, protein synthesis inhibition by interaction with ribosomes, DNA synthesis inhibition (Leal et al, 1999;Thompson and Wannemacher, 1990), and apoptosis by directly affecting cell membrane damage or activation of caspase-3 (Minervini et al, 2005;Ueno et al, 1995), the mechanism of T-2 toxin-induced toxicity is still unknown.…”

Section: Introductionmentioning

confidence: 99%

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

Chen

Cao

Chu

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the effects of T-2 toxin on expressions of Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 on human chondrocytes. Methods: Human chondrocytes were treated with T-2 toxin (1~20 ng/ml) for 5 d. Fas, p53 and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Increases in Fas, p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1~20 ng/ml T-2 toxin, while the expression of the anti-apoptotic factor Bcl-2 was unchanged. Meanwhile, T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner. Conclusion: These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis signaling pathway in human chondrocytes by regulation of apoptosis-related proteins.

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“…69 Toksisitede T-2 toksininin asıl hedefi immün sistemdir. 111 T-2 toksininin majör metaboliti ise HT-2 toksinidir. 112 Avrupa Gıda Güvenliliği Otoritesi [European Food Safety Authority, (EFSA)] 2011 yılında T-2 ve HT-2 toksinleri için yaptığı değerlendirmede, Comet yön-temi kullanılarak DNA hasarının in vitro olarak incelendiği çalışmalardan negatif sonuçların alın-dığını belirtmiştir.…”

Section: Zearalenonlarunclassified

“…113 T-2 toksinin, tiyol grubuna bağlanarak glutatyonu etkisizleştirerek serbest radikal oluşumunu artırdığı, lipit peroksidazı indükleyerek membran stabilitesini bozduğu, apoptozu indüklediği ve DNA, RNA sentezini bozarak protein sentezini inhibe ettiği gösterilmiştir. 111,[114][115][116] Comet yöntemi kullanılarak yapılan bir çalış-mada, T-2 toksininin tavuklarda doz bağımlı olarak DNA hasarına yol açtığı ve genotoksik etki gösterdiği rapor edilmiştir. Ancak, T-2 toksininin genotoksisite mekanizmasının kesin olarak belirlenebilmesi için daha ileri çalışmaların yapılması gerektiği vurgulanmıştır.…”

Section: Zearalenonlarunclassified

Genotoxic Effects of Mycotoxins: Review

Beci̇t¹,

Aydın²,

Baydar³

2017

Turkiye Klinikleri J Pharm Sci

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senobiyotiklere maruziyet sonucunda DNA'da meydana gelen kalıcı değişikliklere "mutasyon" denir. Mutasyon, genotoksik etkinin nihai bir sonucudur. DNA molekülünde oluşan başlıca primer DNA hasarları; DNA sarmalındaki tek ve çift iplik kırıklarını, DNA bazları ve proTurkiye Klinikleri J Pharm Sci 2017;6(2):59-76 59Mikotoksinlerin Genotoksik Etkileri Ö ÖZ ZE ET T Mikotoksinler, hem insan ve hayvan sağlığına olumsuz etkilere hem de ciddi ekonomik kayıplara neden olmaları açısından önemli riskler taşımaktadır. Mikotoksinlere maruziyet, asıl olarak kontamine yem ve gıdaların tüketilmesi ile olup, inhalasyon veya dermal yolla da temas söz konusu olabilmektedir. Mikotoksinler insan sağlığı üzerinde karaciğer, böbrek, bağışıklık, üreme ve gelişme sistemi gibi birçok organ ve sistemi olumsuz yönde etkileyebilmekte, düşük doz ancak kronik maruziyetlerinde özellikle genotoksik ve karsinojenik etkileri ile kansere yol açabilmektedir. Gı-dalarda önemli risk oluşturan mikotoksinler arasında Aspergillus, Penicillium, Fusarium ve Alternaria türlerinin oluşturduğu metabolitler yer almaktadır. Bu metabolitler arasında aflatoksinler, okratoksinler, zearalenon, trikotesenler, fusarium ve yeni keşfedilen fusarium mikotoksinler, patulin, alternaria toksinleri ve ergot alkaloitleri yer almaktadır. Günümüzde bazı mikotoksinlerin genotoksik olduğu artık bilinmektedir. Mikotoksinlerin genotoksik etki mekanizmalarına yönelik araştırmalar halen devam etmektedir. Her ne kadar in vitro çalışmalarda bazı mikotoksinlerin genotoksik etkileri gösterilmiş olsa da bu etkilerin in vivo koşullarla desteklenmesi, etki mekanizmalarının aydınlatılması ve epidemiyolojik çalışmalarla daha ileri değerlendirilmesi gerekmektedir. Bu derleme makalesinde, ekonomik kayıplara yol açan, toplum ve hayvan sağlığı için riskleri olan ve gıda kirleticileri olarak sık karşılaşılan mikotoksinlerin neden olduğu genetik hasarlardan ve bu hasarın olası mekanizmalarından bahsedilecektir.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Aflatoksinler; mutajenler; okratoksinler; mikotoksinler; patulin; mutajenlik testleri; fusarium; alternaria; ergotamin A AB BS S T TR RA AC CT T Mycotoxins have significant risks in terms of their adverse effects on human and animal health and causing serious economic losses. Exposure to mycotoxins is primarily through the consumption of contaminant feed and food, which may be through the inhalation or dermal route. Mycotoxins can adversely affect many organs and systems such as liver, kidney, immune system, reproductive and developmental system on human health. In low dose but chronic exposures, especially it can cause cancer with genotoxic and carcinogenic effects. Mycotoxins reveal significant risks in terms of both adverse effects on human and animal health and serious economic loss. Mycotoxins, which have significant risks in food, include metabolites of Aspergillus, Penicillium, Fusarium and Alternaria species, These metabolites include aflatoxins, ochratoxins, zearalenone, tricothecenes, fusarium and emerged fusarium mycotoxins...

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T-2 toxin immunotoxicity on human B and T lymphoid cell lines

Cited by 63 publications

References 24 publications

The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches

The effect of T-2 toxin on percentages of CD4+, CD8+, CD4+CD8+ and CD21+ lymphocytes, and mRNA expression levels of selected cytokines in porcine ileal Peyer’s patches

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

Genotoxic Effects of Mycotoxins: Review

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