Disruption of liver development and coagulation pathway by ochratoxin A in embryonic zebrafish

Wu, Tzu‐Chin; Lin, Yuting; Huang, Ying-Tzu; Cheng, Ya-Chih; Yu, Feng‐Yih; Liu, Biing-Hui

doi:10.1016/j.taap.2017.12.012

Cited by 21 publications

(16 citation statements)

References 45 publications

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“…An alteration of these genes interferes with the development and function of kidneys and skin (Wu et al 2016). All these factors contributed to the disruption of liver development mediated by OTA (Wu et al, 2018) in the following sequencing: OTA activates miR-731 expression, suppresses PRLRa, and subsequently attenuates p-STAT5 and p-AKT signaling, which implies the final adverse effects on renal development and as endpoint the proliferation and differentiation of embryos.…”

Section: Ochratoxin Amentioning

confidence: 99%

“…Hepatotoxic effects of OTA have been assayed through transcriptomics on zebrafish embryos of strains WT AB and OTA treated (Wu et al, 2018). It was revealed that genes implicated in homeostasis and blood coagulation are downregulated as well as liver markers (f7, f9b, cp and vtna and the liver-specific micro RNA-122 hepatotoxicity marker), which may result in in the alteration of embryo liver size and/or impairment of its development.…”

Section: Ochratoxin Amentioning

confidence: 99%

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Larval zebrafish as an in vitro model for evaluating toxicological effects of mycotoxins

Juan-García

Bind

Engert

2020

Ecotoxicology and Environmental Safety

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The presence of mycotoxins in food has created concern. Mycotoxin prevalence in our environment has changed in the last few years maybe due to climatic and other environmental changes. Evidence has emerged from in vitro and in vivo models: some mycotoxins have been found to be potentially carcinogenic, embryogenically harmful, teratogenic, and to generate nephrotoxicity. The risk assessment of exposures to mycotoxins at early life stages became mandatory. In this regard, the effects of toxic compounds on zebrafish have been widely studied, and more recently, mycotoxins have been tested with respect to their effects on developmental and teratogenic effects in this model system, which offers several advantages as it is an inexpensive and an accessible vertebrate model to study developmental toxicity. External post-fertilization and quick maturation make it sensitive to environmental effects and facilitate the detection of endpoints such as morphological deformities, time of hatching, and behavioral responses. Therefore, there is a potential for larval zebrafish to provide new insights into the toxicological effects of mycotoxins. We provide an overview of recent mycotoxin toxicological research in zebrafish embryos and larvae, highlighting its usefulness to toxicology and discuss the strengths and limitations of this model system.

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Section: Ochratoxin Amentioning

confidence: 99%

Section: Ochratoxin Amentioning

confidence: 99%

Larval zebrafish as an in vitro model for evaluating toxicological effects of mycotoxins

Juan-García

Bind

Engert

2020

Ecotoxicology and Environmental Safety

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“…In compliance with these directives Dr. Gregory Penner of NeoVentures developed an aptamer-based Ochratoxin A (OTA) detection kit for commercial application in agro-food industry (Penner, 2012 ). OTA is a mycotoxin that not only impairs blood coagulation (Wu et al, 2018 ), but is also a potential carcinogen (Pfohl-Leszkowicz and Manderville, 2007 ) produced by fungus in contaminated food products. Pioneering work by Penner's group evolved highly sensitive (~200 nM K d ) and specific 36 nt aptamer with potential to detect ppb quantities of OTA in naturally contaminated wheat samples (Cruz-Aguado and Penner, 2008 ).…”

Section: Success Studies Of Aptamers In Diagnosticsmentioning

confidence: 99%

Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity

Kalra

Dhiman

Cho

et al. 2018

Front. Mol. Biosci.

126

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Aptamers are structured nucleic acid molecules that can bind to their targets with high affinity and specificity. However, conventional SELEX (Systematic Evolution of Ligands by EXponential enrichment) methods may not necessarily produce aptamers of desired affinity and specificity. Thus, to address these questions, this perspective is intended to suggest some approaches and tips along with novel selection methods to enhance evolution of aptamers. This perspective covers latest novel innovations as well as a broad range of well-established approaches to improve the individual binding parameters (aptamer affinity, avidity, specificity and/or selectivity) of aptamers during and/or post-SELEX. The advantages and limitations of individual aptamer selection methods and post-SELEX optimizations, along with rational approaches to overcome these limitations are elucidated in each case. Further the impact of chosen selection milieus, linker-systems, aptamer cocktails and detection modules utilized in conjunction with target-specific aptamers, on the overall assay performance are discussed in detail, each with its own advantages and limitations. The simple variations suggested are easily available for facile implementation during and/or post-SELEX to develop ultrasensitive and specific assays. Finally, success studies of established aptamer-based assays are discussed, highlighting how they utilized some of the suggested methodologies to develop commercially successful point-of-care diagnostic assays.

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“…The reduced liver size with hepatocytes having large‐sized clear vacuoles and peripheral nucleus, sunken cytoplasmic spaces and augmented nucleus to cytoplasmic are the major changes in OTA toxicity. It is responsible for hepatotoxicity at early stages of development in zebrafish (Wu et al, 2018). The findings were more or less similar to the studies performed on rodent models, in which oxidative stress and liver necrosis were observed as a result of vacuolated degeneration due to OTA (Aydm, Ozçelik, Cicek, & Soyöz, 2003; Nussbaum et al, 2013).…”

Section: Liver Injury Models In Zebrafishmentioning

confidence: 99%

Zebrafish: An emerging model system to study liver diseases and related drug discovery

Katoch

Patial

2020

J of Applied Toxicology

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The zebrafish has emerged as a powerful vertebrate model for studying liverassociated disorders. Liver damage is a crucial problem in the process of drug development and zebrafish have proven to be an important tool for the highthroughput screening of drugs for hepatotoxicity. Although the structure of the zebrafish liver differs to that of mammals, the fundamental physiologic processes, genetic mutations and manifestations of pathogenic responses to environmental insults exhibit much similarity. The larval transparency of the zebrafish is a great advantage for real-time imaging in hepatic studies. The zebrafish has a broad spectrum of cytochrome P450 enzymes, which enable the biotransformation of drugs via similar pathways as mammals, including oxidation, reduction and hydrolysis reactions. In the present review, we appraise the various drugs, chemicals and toxins used to study liver toxicity in zebrafish and their similarities to the rodent models for liverrelated studies. Interestingly, the zebrafish has also been effectively used to study the pathophysiology of nonalcoholic and alcoholic fatty liver disease. The genetic models of liver disorders and their easy manipulation provide great opportunity in the area of drug development. The zebrafish has proven to be an influential model for the hepatic system due to its invertebrate-like advantages coupled with its vertebrate biology. The present review highlights the pivotal role of zebrafish in bridging the gap between cell-based and mammalian models.

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Disruption of liver development and coagulation pathway by ochratoxin A in embryonic zebrafish

Cited by 21 publications

References 45 publications

Larval zebrafish as an in vitro model for evaluating toxicological effects of mycotoxins

Larval zebrafish as an in vitro model for evaluating toxicological effects of mycotoxins

Simple Methods and Rational Design for Enhancing Aptamer Sensitivity and Specificity

Zebrafish: An emerging model system to study liver diseases and related drug discovery

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