Ochratoxin a-induced hepatotoxicity through phase i and phase ii reactions regulated by ahr in liver cells

Hye Soo Shin, Hyun Jung Lee, Min Cheol Pyo, Dojin Ryu, Kwang Won Lee

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)


Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress.

Original languageEnglish
Article number377
Issue number7
Publication statusPublished - 2019 Jul

Bibliographical note

Funding Information:
Funding: This research was funded by the International Joint R&D Program, Agency for Korean National Food Cluster (Q1624241), Korean University Grant (K1803651).

Publisher Copyright:
© 2019 by the authors.


  • Hepatotoxicity
  • Ochratoxin A
  • Oxidative stress
  • Phase I reaction
  • Phase II reaction

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis


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