Ochratoxin A triggered intracerebral hemorrhage in embryonic zebrafish: Involvement of microRNA-731 and prolactin receptor

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

doi:10.1016/j.chemosphere.2019.125143

Cited by 17 publications

(7 citation statements)

References 47 publications

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“…This exposure time and concentration approximates the median lethality in zebrafish embryos. Moreover, accompanying the observed toxicity, relevant organ systems including CNS, gastrointestinal system and liver (as previously reported targets of OTA 18 , 20 , 24 , 29 , 30 ) are generally differentiated at this developmental stage, and loss of the chorion as a potential barrier to OTA uptake following hatching generally occurs, likewise, at approximately 72 hpf. Exposure of embryos at this development stage in subsequent aspects of the study, therefore, enabled both improved uptake potential (i.e., post-hatch loss of chorion), and assessment of the possible targeting of these fully differentiated organ systems.…”

Section: Resultssupporting

confidence: 69%

“…The observation of increased ROS (and concurrent localization of OTA) to the distal brain region, on the other hand, suggests presumptively independent targeting of the CNS. In fact, both damage to the brain (e.g., hemorrhaging), as well as neurodevelopmental and neurobehavioral effects, have been previously reported for OTA in the zebrafish embryo model 18 , 24 and other systems 35 . In the present study, however, N -acetylaspartate (NAA), which is found exclusively in neural cells, and is an established biomarker of neural damage 53 , previously linked to neurotoxicity in the zebrafish embryo model 27 , was not altered with exposure to OTA (Fig.…”

Section: Resultsmentioning

confidence: 83%

“…Early life stages (i.e., embryos and larvae) of the zebrafish ( Danio rerio ) have become widely established as a toxicological model for a range of environmental toxicants including mycotoxins and, indeed, OTA 17 – 21 . Several previous studies have characterized OTA toxicity, typically in the sub-micromolar range, in embryo and larval stages of the zebrafish including acute lethality, developmental dysfunction and neurobehavioral effects, as well as toxin-specific targets including hepatoxicity and nephrotoxicity 17 – 20 , 22 – 24 . The capacity of this model system is potentiated not only by the availability of a wide range of scorable toxicological endpoints, but also a growing range of biochemical and molecular technologies including “omics” approaches which have been adapted to zebrafish embryos and larvae 25 .…”

Section: Introductionmentioning

confidence: 99%

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An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling

Eeza

Bashirova

Zuberi

et al. 2022

Sci Rep

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Ochratoxin A (OTA) is one of the most widespread mycotoxin contaminants of agricultural crops. Despite being associated with a range of adverse health effects, a comprehensive systems-level mechanistic understanding of the toxicity of OTA remains elusive. In the present study, metabolic profiling by high-resolution magic angle spinning (HRMAS) NMR, coupled to intact zebrafish embryos, was employed to identify metabolic pathways in relation to a systems-level model of OTA toxicity. Embryotoxicity was observed at sub-micromolar exposure concentrations of OTA. Localization of OTA, based on intrinsic fluorescence, as well as a co-localization of increased reactive oxygen species production, was observed in the liver kidney, brain and intestine of embryos. Moreover, HRMAS NMR showed significant alteration of metabolites related to targeting of the liver (i.e., hepatotoxicity), and pathways associated with detoxification and oxidative stress, and mitochondrial energy metabolism. Based on metabolic profiles, and complementary assays, an integrated model of OTA toxicity is, thus, proposed. Our model suggests that OTA hepatotoxicity compromises detoxification and antioxidant pathways, leading to mitochondrial membrane dysfunction manifested by crosstalk between pathways of energy metabolism. Interestingly, our data additionally aligns with a possible role of mitochondrial fusion as a “passive mechanism” to rescue mitochondrial integrity during OTA toxicity.

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Section: Resultssupporting

confidence: 69%

Section: Resultsmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling

Eeza

Bashirova

Zuberi

et al. 2022

Sci Rep

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“…Following OTA exposure in piglets, upregulation of miR-497, miR-133a-3p, miR-423-3p, miR-34a, and miR-542-3p and downregulation of miR-421-3p, miR-490, and miR-9840-3p altered miRNA connect to different biological pathways, suggesting that these miRNAs could be a biomarker of OTA toxicity ( 77 ). In zebrafish embryos, OTA inhibits the prolactin receptor (PrLRA) and causes brain bleeding by acting on miR-731 ( 78 ). AFB1 can significantly boost the expression of miR-33a-5p in HepG2 and block the Wnt/β-catenin signaling pathway, according to several studies ( 79 ).…”

Section: Principal Toxicological Mechanisms Induced By Mycotoxinsmentioning

confidence: 99%

Protective and detoxifying effects conferred by selenium against mycotoxins and livestock viruses: A review

Fang

Liu

2022

Front. Vet. Sci.

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Animal feed can easily be infected with molds during production and storage processes, and this can lead to the production of secondary metabolites, such as mycotoxins, which eventually threaten human and animal health. Furthermore, livestock production is also not free from viral infections. Under these conditions, the essential trace element, selenium (Se), can confer various biological benefits to humans and animals, especially due to its anticancer, antiviral, and antioxidant properties, as well as its ability to regulate immune responses. This article reviews the latest literature on the antagonistic effects of Se on mycotoxin toxicity and viral infections in animals. We outlined the systemic toxicity of mycotoxins and the primary mechanisms of mycotoxin-induced toxicity in this analysis. In addition, we pay close attention to how mycotoxins and viral infections in livestock interact. The use of Se supplementation against mycotoxin-induced toxicity and cattle viral infection was the topic of our final discussion. The coronavirus disease 2019 (COVID-19) pandemic, which is currently causing a health catastrophe, has altered our perspective on health concerns to one that is more holistic and increasingly embraces the One Health Concept, which acknowledges the interdependence of humans, animals, and the environment. In light of this, we have made an effort to present a thorough and wide-ranging background on the protective functions of selenium in successfully reducing mycotoxin toxicity and livestock viral infection. It concluded that mycotoxins could be systemically harmful and pose a severe risk to human and animal health. On the contrary, animal mycotoxins and viral illnesses have a close connection. Last but not least, these findings show that the interaction between Se status and host response to mycotoxins and cattle virus infection is crucial.

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“…From a chemical point of view, OTA is a phenylalanyl derivative of a substituted isocoumarin, referred to as (R)-N-[(5-Chloro-3,4-dihydro-8-hydroxy-3-methyl-1-oxo-1H-2-benzopyran-7-yl)-carbonyl]-L -phenylalanine ( Figure 1). OTA is the most toxic member of the ochratoxins group [3] and it is among the mycotoxins that are of biggest concern for food and feed safety due to many adverse effects on humans and animals [4,5]. For example, nephrotoxicity, immunotoxicity, and carcinogenicity have been described among the possible elicited effects.…”

Section: Introductionmentioning

confidence: 99%

An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme

Dellafiora

Gonaus²,

Streit³

et al. 2020

Toxins

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Ochratoxin A (OTA), a mycotoxin that is of utmost concern in food and feed safety, is produced by fungal species that mainly belong to the Aspergillus and Penicillium genera. The development of mitigation strategies to reduce OTA content along the supply chains is key to ensuring safer production of food and feed. Enzyme-based strategies are among the most promising methods due to their specificity, efficacy, and multi-situ applicability. In particular, some enzymes are already known for hydrolyzing OTA into ochratoxin alpha (OTα) and phenylalanine (Phe), eventually resulting in detoxification action. Therefore, the discovery of novel OTA hydrolyzing enzymes, along with the advancement of an innovative approach for their identification, could provide a broader basis to develop more effective mitigating strategies in the future. In the present study, a hybrid in silico/in vitro workflow coupling virtual screening with enzymatic assays was applied in order to identify novel OTA hydrolyzing enzymes. Among the various hits, porcine carboxypeptidase B was identified for the first time as an effective OTA hydrolyzing enzyme. The successful experimental endorsement of findings of the workflow confirms that the presented strategy is suitable for identifying novel OTA hydrolyzing enzymes, and it might be relevant for the discovery of other mycotoxin- mitigating enzymes.

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Ochratoxin A triggered intracerebral hemorrhage in embryonic zebrafish: Involvement of microRNA-731 and prolactin receptor

Cited by 17 publications

References 47 publications

An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling

An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling

Protective and detoxifying effects conferred by selenium against mycotoxins and livestock viruses: A review

An In Silico Target Fishing Approach to Identify Novel Ochratoxin A Hydrolyzing Enzyme

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