Metabolic Pathways of T-2 Toxin in in Vivo and in Vitro Systems of Wistar Rats

Yang, Shupeng; Li, Yanshen; Cao, Xingyuan; Hu, Dewei; Wang, Zhanhui; Wang, Ying; Shen, Jianzhong; Zhang, Suxia

doi:10.1021/jf4012054

Cited by 37 publications

(57 citation statements)

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“…All the manipulation was in compliance with Chinese laws and guidelines (GKFCZ2001545) and accorded to the China Agricultural University regulations concerning protection of animals used for scientific purposes (2010-SYXK-0037). Hepatic microsomes were prepared according to the procedure reported by Yang et al [26,27]. The protein content of the microsomes was estimated according to Lowry et al using crystalline bovine serum albumin as the control standard [32].…”

Section: Preparation Of Liver Microsomesmentioning

confidence: 99%

“…In recent years, liver microsomes have been extensively utilized in drug metabolism studies because of their lower cost, good reproducibility, and simple preparation [26][27][28]34]. In order to rapidly characterize the metabolism of OTA, rat liver microsomes were incubated with OTA and NADPH.…”

Section: Identification Of Ota Metabolites In Rat Liver Microsomesmentioning

confidence: 99%

“…Currently, liquid chromatography combined with mass spectrometry (LC-MS) is playing an important role in the area of metabolite identification. In particular, ultraperformance liquid chromatography-quadrupole/time-offlight tandem mass spectrometry (UPLC-Q/TOF-MS) became an increasingly popular technique to identify unknown compounds, due to its high speed, superior selectivity, large sensitivity, and mass accuracy [26][27][28][29][30][31]. To completely characterize the OTA metabolites, the metabolism of OTA in liver microsomes of rats, chickens, swine, goats, cows, and humans was compared using UPLC-Q/TOF-MS.…”

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

et al. 2015

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Ochratoxin A (OTA) is a mycotoxin that frequently contaminates a wide variety of food and feedstuffs. The metabolism of OTA greatly affects fate and toxicity in humans and animals, because of its possible carcinogenic character (International Agency for Research on Cancer (IARC), group 2B). To completely characterize the metabolites of OTA, the metabolism of OTA in liver microsomes of rats, chickens, swine, goats, cows, and humans was investigated using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UPLC-Q/TOF-MS). In addition, an in vivo comparative metabolism study of OTA was performed among rats and chickens after oral administration of OTA. As a result, a clear metabolic profile of OTA in different species was proposed, and a total of eight metabolites were identified, of which three hydroxylated metabolites at the phenylalanine moiety were discovered for the first time (preliminarily identified as 9'-OH-OTA, 7'-OH-OTA, and 5'-OH-OTA). Considerable amounts of 7'-OH-OTA were detected in different species' liver microsomes, especially in chickens and humans. Moreover, the metabolism of OTA in chickens was elucidated for the first time in the present study. The 7'-OH-OTA proved to be the main metabolite in vitro and in vivo in chickens. Furthermore, the 4(S)-OH-OTA isomer was the major one, and 4(R)-OH-OTA the minor metabolite in chickens, which was different from others where 4R was the major. OTA undergoes metabolism via three different pathways, namely hydroxylation, dechlorination, and conjugation. The proposed metabolic pathways of OTA in various species provide the scientific community useful data for the toxicological safety evaluation of OTA among different species, and will further facilitate the food safety evaluation of OTA.

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Section: Preparation Of Liver Microsomesmentioning

confidence: 99%

Section: Identification Of Ota Metabolites In Rat Liver Microsomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

et al. 2015

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“…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. Ayrıca, 2001 yılından bu yana T-2 toksininin sitogenetik hasarına dair yeni bir veri olmadığı, T-2 toksininin genotoksik etkisi üze-rine epidemiyolojik bir kanıtın bulunmadığı ve Ames, mikroçekirdek, kromozomal sapma testlerinde negatif sonuçlandığı bilgisi yer almaktadır.…”

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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“…Hepatic microsomes were prepared from the homogenized livers of untreated animals (rats, chickens, swine, goats, and cows) by differential centrifugation, according to the procedure reported by Yang et al [26][27][28][29]. Microsomes and cytosol were frozen in liquid nitrogen, then stored at −80°C until use.…”

Section: Preparation Of Liver Microsomesmentioning

confidence: 99%

Unraveling the in vitro and in vivo metabolism of diacetoxyscirpenol in various animal species and human using ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

Yang¹,

Boevre

Zhang³

et al. 2015

Anal Bioanal Chem

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Diacetoxyscirpenol (DAS), a Fusarium mycotoxin belonging to the trichothecene type A mycotoxins, is able to contaminate food and feed worldwide. Only limited information is available regarding the metabolism of DAS. The present study used ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry (UHPLC-Q/TOF) to investigate the in vitro phase I and II metabolism of DAS by rat, chicken, swine, goat, cow, and human liver microsomes. An extensive metabolization profile of DAS has been observed. A total of seven phase I and three phase II metabolites of DAS were detected. Among the identified molecules, four phase I metabolites (8β-hydroxy-DAS, neosolaniol, 7-hydroxy-DAS, and its epimer) and two phase II metabolites (4-deacetyl-DAS-3-glucuronic acid and 4-deacetyl-DAS-4-glucuronic acid) were identified for the first time. These results indicate that the major metabolic pathways of DAS in vitro were hydrolyzation (M1-M3), hydroxylation (M4-M7), and conjugation (M8-M10). Qualitative differences in phase I and II metabolic profiles of DAS between the five animal species and human were observed. 4-Deacetyl-DAS was the primary metabolite from liver microsomes of all species, especially human. The in vivo metabolism of DAS in rats and chickens after oral administration of DAS was also investigated and compared. The major metabolites for rats and chickens were 4-deacetyl-DAS and 7-hydroxy-DAS. These results will help to gain a more detailed insight into the metabolism and toxicity of DAS among different animal species and human. Graphical Abstract The metabolism of diacetoxyscirpenol in farm animals and human.

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Metabolic Pathways of T-2 Toxin in in Vivo and in Vitro Systems of Wistar Rats

Cited by 37 publications

References 37 publications

In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

Genotoxic Effects of Mycotoxins: Review

Unraveling the in vitro and in vivo metabolism of diacetoxyscirpenol in various animal species and human using ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry

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