Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells

Chaudhari, Manjari; Ravindran, Jayaraj; Bhaskar, A.S.B.; Rao, P. Venkata

doi:10.1016/j.tox.2009.06.002

Cited by 153 publications

(91 citation statements)

References 35 publications

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“…However, results published on the effects of T-2 toxin on lipid peroxidation are contradictious. T-2 toxin-induced oxidative stress was found in vitro in chondrocytes (He et al, 2012) and in human cervical cancer cells (Chaudhari et al, 2009a) and in vivo in mice (Chaudhari et al, 2009b), rats (Rizzo et al, 1994;Rocha et al, 2005) and broiler chickens (Mézes et al, 1998;Dvorska et al, 2007) in a dose dependent manner. Most of the previous studies also revealed that T-2 toxin has marked effect on the antioxidant status of animals (Atroshi et al, 2002, Surai, 2002 because of its pro-oxidant properties (Rizzo et al, 1994).…”

Section: Introductionmentioning

confidence: 98%

Effects of Long-term Feeding of Graded Levels of T-2 Toxin-contaminated Diets on Performance, Some Lipid Peroxide and Glutathione Redox Status Parameters of Broiler Chickens

et al. 2015

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The effect of two different contamination levels of T-2 toxin (1.5 or 3.4 mg/kg feed) was investigated in a 28-days feeding trial on body weight, relative weight of liver and spleen, and some lipid peroxidation and glutathione redox parameters of 14-days old broiler chicken. The results showed that T-2 toxin decreased significantly the body weight at both contamination levels and showed a dose-dependent tendency. Relative weight of liver increased till the end of the trial, while relative weight of spleen was lower at both samplings at lower level of T-2 toxin exposure. Initial phase of lipid peroxidation (conjugated dienes and trienes) was not detected in the liver, but as product of later phase, thiobarbituric acid reactive substances increased significantly, except in the liver. Glutathione content on day 14 was higher in liver homogenate as compared to the control at the lower T-2 toxin contamination level. On day 28 it was higher in blood plasma at the higher and in liver homogenate at both levels of T-2 contamination. Glutathione peroxidase activity on day 14 was significantly higher in liver and spleen homogenates as compared to the control at the lower level of T-2 toxin contamination. On day 28, significantly higher activity was found at both T-2 toxin contamination levels in liver homogenate, and at the lower contamination level in spleen homogenate as compared to the control.The results revealed that T-2 toxin exposure initiates lipid peroxidation and activates the glutathione redox system as well, but the changes were irrespective of the dose-and partly duration of the exposure.

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Section: Introductionmentioning

confidence: 98%

Effects of Long-term Feeding of Graded Levels of T-2 Toxin-contaminated Diets on Performance, Some Lipid Peroxide and Glutathione Redox Status Parameters of Broiler Chickens

et al. 2015

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“…Some researchers believe that T-2 induces oxidative stress, leading to the activation of different pathways and apoptosis (47). Consistent with this speculation, pathway analysis indicated that many genes involved in mitochondrial respiratory function were altered by T-2.…”

Section: T-2 Toxin Biotransformationmentioning

confidence: 78%

Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes

Wang

Jiang

Zhang

et al. 2011

Molecular & Cellular Proteomics

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Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of countermeasures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and

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“…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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Oxidative stress induction by T-2 toxin causes DNA damage and triggers apoptosis via caspase pathway in human cervical cancer cells

Cited by 153 publications

References 35 publications

Effects of Long-term Feeding of Graded Levels of T-2 Toxin-contaminated Diets on Performance, Some Lipid Peroxide and Glutathione Redox Status Parameters of Broiler Chickens

Effects of Long-term Feeding of Graded Levels of T-2 Toxin-contaminated Diets on Performance, Some Lipid Peroxide and Glutathione Redox Status Parameters of Broiler Chickens

Integrated Transcriptional and Proteomic Analysis with In Vitro Biochemical Assay Reveal the Important Role of CYP3A46 in T-2 Toxin Hydroxylation in Porcine Primary Hepatocytes

Genotoxic Effects of Mycotoxins: Review

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