DNA damage in organs of mice treated acutely with patulin, a known mycotoxin

Melo, Flávia Terezinha de; Oliveira, Iuri Marques de; Greggio, Samuel; Costa, Jaderson Costa da; Guecheva, Temenouga Nikolova; Saffi, Jenifer; Henriques, João Antônio Pêgas; Rosa, Renato Moreira

doi:10.1016/j.fct.2011.12.022

Cited by 74 publications

(32 citation statements)

References 64 publications

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“…Contamination of food with patulin causes gastrointestinal inflammation, ulcers, and bleeding (McKinley et al 1982). The mutagenicity (Pfeiffer et al 1998;de Melo et al 2012), embryotoxicity (Roll et al 1990;Wu et al 2005), and carcinogenicity (Dickens and Jones 1961) of patulin have also been reported. In addition, it is highly reactive towards the thiol groups of proteins and glutathione (Puel et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Katsuyama

Konno

Shimoyama

et al. 2014

Tohoku J. Exp. Med.

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Patulin is a mycotoxin that is found mainly in apple products and causes symptoms such as bleeding from the digestive tract and diarrhea. Efforts to elucidate the mechanism of its toxicity have focused on protein tyrosine phosphatases (PTPs), which regulate the function of tight junctions (TJs) in colon epithelial cells. Patulin reacts with the conserved cysteine residues in the catalytic domains of PTP isoforms. Treatment of Caco-2 human colon cancer cells, used as a colon epithelial model, with 50 µM patulin decreased the level of density-enhanced phosphatase-1 (DEP-1) protein to 30% of the control level after 6 h. The level of DEP-1 mRNA was also decreased during 24 h after treatment with patulin. Moreover, knockdown of DEP-1 increased the level of phosphorylated claudin-4. Destruction of TJs by patulin treatment was observed by immunostaining with an antibody against zonula occludens (ZO)-1. To better understand the mechanistic basis of the decrease in DEP-1 mRNA levels, we searched for a cis-element upstream of the DEP-1 gene and found an element responsive to the peroxisome proliferator-activated receptor gamma (PPARγ ) protein. Using a PPARγ-specific antibody, we showed a decrease in PPARγ abundance to 42% of the control level within 6 h after treatment with patulin. PPARγ has four cysteine residues that are involved in zinc finger formation. Our data suggest that DEP-1 affects TJ function and that PPARγ might control DEP-1 expression. Therefore, the toxicity of patulin to cellular functions might be attributable to its ability to down-regulate the expression of DEP-1 and PPARγ.

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Section: Introductionmentioning

confidence: 99%

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Katsuyama

Konno

Shimoyama

et al. 2014

Tohoku J. Exp. Med.

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“…The induction of PUMA and BID by LGG could be due to the damage effect caused by the exposure of cells to patulin or the increase in cells proliferation caused by LGG leading to cytotoxicity by the HepG2 cells themselves, which correlates with our finding of LGG producing increasing cell proliferation (Figure 3). Patulin is known to induce DNA damage leading to p53 mediated cell cycle arrest (Saxena et al, 2009;de Melo et al, 2012). It has been proven that p53 induces apoptosis by converting a few target genes, including certain BCL-2 family members, and also by directly targeting mitochondria.…”

Section: Cell Damage Induced By Puma and Bidmentioning

confidence: 99%

“…Patulin has also been found to be teratogenic, carcinogenic, genotoxic, and mutagenic causing DNA damage in certain cases (Ciegler, Becwith, & Jackson, 1976Osswald, Komitowski, & Winter, 1978, Zhou, Jiang, Geng, Cao, & Zhong, 2009. Previous studies have shown that patulin could induce oxidative DNA damage in many organ areas including liver, kidney, brain, and urinary bladder (de Melo et al, 2012). Patulin has also been found to be genotoxic and mutagenic in Chinese hamster lung fibroblast V79 cells, and hepatoma cells HepG2 (Ayed-Boussema et al, 2013de Vrese, Kristen, Rautenberg, Laue, & Schrezenmeir, 2011;Ejtahed et al 2011;Khani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus rhamnosus GG Inhibits BID Dependent-Apoptosis in Human Hepatocellular Carcinoma Cells Exposed to Patulin

Karlton-Senaye¹,

Bansode²,

Randolph³

et al. 2017

JFR

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Patulin, a mycotoxin, which is a major contaminant in apple juices, has contributed immensely to the occurrence of liver diseases. Consumption of apple juice could over long period of time become harmful to the health of individuals with pre-existing liver disease. Probiotics are known for their role in patulin removal from aqueous media. In this study, we investigated the effects of a probiotic microorganism on patulin toxicity in hepatocellular carcinoma (HepG2) cells and established the protective effect of Lactobacillus rhamnosus (LGG) as mediated by induction of BH3-interacting domain antagonist (BID) in response to patulin toxicity. After 24 hours of patulin exposure followed by 24 hours of treatment with Lactobacillus rhamnosus, cells proliferation decreased with increasing patulin exposure in samples without LGG pre-treatment, whereas with increasing concentration of patulin, cells were relatively rescued in LGG treated samples. It was further observed that pre-treatment of LGG with polysaccharide gums led to a decline in cell proliferation with increasing patulin exposure. Compare to the control, the expression of p53 upregulated moderator of apoptosis (PUMA) increased slightly by 7 % at 10µM patulin exposure in treatment and decreased by 30% in untreated cell. However, the expression of BID decreased by 26% in treatment compared to the control. We further established that the protective effect of Lactobacillus rhamnosus was mediated by the inhibition of BID. Our findings suggest that Lactobacillus rhamnosus GG could potentially function as a therapeutic agent to reverse the damaging effect of patulin on the liver of individuals with pre-existing liver disease.

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“…146,150 PAT elektrofilik yapısı nedeni ile nükleo-filik gruplara saldırır. Yapısında sistein proteini bulunan ve hücrenin hasara karşı korunmasında önemli rolü olan glutatyon dâhil çeşitli proteinlerin ve DNA'nın yapısını kalıcı olarak değiştirerek sitotoksisiteye ve genotoksisiteye yol açabileceği ileri sürülmektedir.…”

unclassified

“…22 PAT'nin sülfidril gruplarına olan afinitesi nedeniyle artan mikroçekirdek ve nükloplazmik köprü oluşumu ve DNA çapraz bağlanmaları ile kromozomal hasara neden olduğu bildirilmiş-tir. 147,[150][151][152][153] Tiyol gruplarına olan afinitesi nedeni ile glutatyonu azaltması sonucu SOR'yi artırdığı ve böylece oksidatif strese yol açarak, insan hücrele-rinde sitotoksisiteye ve kromozom kırıklarına yol açarak genotoksisiteye neden olduğu gösterilmiş-tir. Toksik etkilerin moleküler düzeyde araştırıl-ması sonucunda, PAT toksisitesinde özgül bir protein olan kinazın rolü olduğu gösterilmiştir.…”

unclassified

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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DNA damage in organs of mice treated acutely with patulin, a known mycotoxin

Cited by 74 publications

References 64 publications

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

The Mycotoxin Patulin Decreases Expression of Density-Enhanced Phosphatase-1 by Down-Regulating PPAR<i>γ</i> in Human Colon Cancer Cells

Lactobacillus rhamnosus GG Inhibits BID Dependent-Apoptosis in Human Hepatocellular Carcinoma Cells Exposed to Patulin

Genotoxic Effects of Mycotoxins: Review

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