Renal toxicity through AhR, PXR, and Nrf2 signaling pathway activation of ochratoxin A-induced oxidative stress in kidney cells

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Because ochratoxin A (OTA) is widely found in foods, people are susceptible to OTA exposure. The mechanism leading to renal toxicity induced by OTA remains unclear. The aim of this study was to investigate OTA-induced toxicity in human proximal tubule HK-2 cells. OTA decreased cell viability, and the expression of kidney injury molecule-1 (KIM-1), a kidney damage marker, was increased when HK-2 cells were exposed to OTA. Additionally, OTA treatment of cells increased intracellular reactive oxygen species and malondialdehyde and decreased glutathione levels. OTA-treated cells induced the aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) genes followed by induction of the cytochrome P450 1A1 (CYP1A1), CYP1A2, and CYP3A4 genes representing phase I enzyme. The mRNA expression of phase II enzymes such as heme oxygenase-1, nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1, and glutamate cysteine ligase catalytic subunit were upregulated by activation of NF-E2-related factor 2 (Nrf2) translocation by treatment with OTA. The response of OTA-orally administered mice also showed marked increases in these enzymes as well as KIM-1. These results indicate that OTA induces phase I and II enzymes through the AhR, PXR, and Nrf2 signaling pathways in HK-2 cells, which may lead to modulation of proximal tubule injury.

Original languageEnglish
Pages (from-to)59-68
Number of pages10
JournalFood and Chemical Toxicology
Volume122
DOIs
Publication statusPublished - 2018 Dec 1

    Fingerprint

Keywords

  • Aryl hydrocarbon receptor
  • Kidney injury
  • NF-E2-related factor 2
  • Ochratoxin A
  • Oxidative stress
  • Pregnane X receptor

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this