Exposure to Ochratoxin A: Detection, Mitigation and Mechanisms of Toxicity

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Mycotoxins".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 3305

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Department of Chemistry and Toxicology, University of Guelph, Guelph, Ontario, N1G 2W1, Canada
Interests: DNA damage by phenolic toxins including ochratoxin A; Modified DNA bases as fluorescent probes
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Special Issue Information

Dear Colleagues,

In the seminal paper published in Nature, 1965, van Der Merwe, Steyn, Fourie, Scott and Theron, reported the isolation of a new toxic metabolite, called ochratoxin A (now abbreviated OTA), from Aspergillus ochraceus. The mycotoxin contains a chlorophenolic moiety amide-linked to L-phenylalanine and exhibits strong blue fluorescence, which has played a key role in self-signaling detection of OTA in complex matrices.   Experimental carcinogenicity studies in rodent models carried out in the 1980s demonstrated OTA to be a potent kidney carcinogen.  OTA is regarded as the most toxic member of the ochratoxins, which have attracted considerable attention since they are one of the most abundant food-contaminating mycotoxins in the world and are classified as potentially carcinogenic to humans (Group 2B). Ongoing interdisciplinary research on the ochratoxins have been concerned with detection in feed and human foodstuff, occurrence and estimation of dietary and inhalation intake, establishment of limits for human consumption based on risk assessment, understanding mechanisms of toxicity for the development of detoxification processes and determining the toxic effects of OTA in the presence of other mycotoxins. Recent highlights in OTA research include the development of aptasensor-based platforms that eliminate the need for complex instrumentation to deliver rapid, on-site detection, and formation of new OTA bioconjugates for immunodiagnostics.  We hope that this collection of Toxins entitled “Exposure to Ochratoxin A: Detection, Mitigation and Mechanisms of Toxicity” will provide the readership with a better understanding of the key issues being addressed at the present time.

Prof. Dr. Richard A. Manderville
Guest Editor

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Keywords

  • Ochratoxin A (OTA)
  • OTA occurrence
  • OTA detection
  • OTA mitigation
  • risk assessment
  • OTA biosynthesis

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Published Papers (1 paper)

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Research

16 pages, 4319 KiB  
Article
Anti-Apoptotic Effect of Flavokawain A on Ochratoxin-A-Induced Endothelial Cell Injury by Attenuation of Oxidative Stress via PI3K/AKT-Mediated Nrf2 Signaling Cascade
by Peramaiyan Rajendran, Abdullah M. Alzahrani, Vishnu Priya Veeraraghavan and Emad A. Ahmed
Toxins 2021, 13(11), 745; https://doi.org/10.3390/toxins13110745 - 21 Oct 2021
Cited by 14 | Viewed by 2698
Abstract
This study investigates the endothelial protective activity of flavokawain A (FKA) against oxidative stress induced by ochratoxin A (OTA), which acts as a mycotoxin, and its primary mechanisms in in vitro models. Reactive oxygen species, in general, regulate oxidative stress that significantly contributes [...] Read more.
This study investigates the endothelial protective activity of flavokawain A (FKA) against oxidative stress induced by ochratoxin A (OTA), which acts as a mycotoxin, and its primary mechanisms in in vitro models. Reactive oxygen species, in general, regulate oxidative stress that significantly contributes to the pathophysiology of endothelial dysfunctions. OTA exerts toxicity through inflammation and the accumulation of ROS. This research is aimed at exploring the defensive function of FKA against the endothelial injury triggered by OTA through the Nrf2 pathway regulated by PI3K/AKT. OTA exposure significantly increased the nuclear translocation of NFκB, whereas we found a reduction in inflammation via NFκB inhibition with FKA treatment. FKA increased the PI3K and AKT phosphorylation, which may lead to the stimulation of antioxidative and antiapoptotic signaling in HUVECs. It also upregulated the phosphorylation of Nrf2 and a concomitant expression of antioxidant genes, such as HO-1, NQO-1, and γGCLC, depending on the dose under the oxidative stress triggered by OTA. Knockdown of Nrf2 through small interfering RNA (siRNA) impedes the protective role of FKA against the endothelial toxicity induced by OTA. In addition, FKA enhanced Bcl2 activation while suppressing apoptosis marker proteins. Therefore, FKA is regarded as a potential agent against endothelial oxidative stress caused by the deterioration of the endothelium. The research findings showed that FKA plays a key role in activating the p-PI3K/p-AKT and Nrf2 signaling pathways, while suppressing caspase-dependent apoptosis. Full article
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