Toxins 2014, 6(1), 371-379; doi:10.3390/toxins6010371
Review

A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity

Received: 11 November 2013; in revised form: 10 January 2014 / Accepted: 14 January 2014 / Published: 20 January 2014
(This article belongs to the Special Issue Recent Advances in Ochratoxins Research)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Several studies have demonstrated that ochratoxin A (OTA) inhibits the nuclear factor, erythroid 2-like 2 (Nrf2) oxidative stress response pathway. At the cellular level this would attenuate (i) glutathione synthesis; (ii) recycling of oxidised glutathione; (iii) activity of oxidoreductases; and (iv) phase II metabolism inducibility. The effects combined would render the cell and tissue more vulnerable to oxidative stress. Indeed, Nrf2 knock out animals exhibit increased susceptibility to various types of chemical-induced injury. Several studies have shown that OTA exposure can inhibit Nrf2 responses. Such an action would initially lead to increased susceptibility to both physiological and chemical-induced cell stress. However, chronic exposure to OTA may also act as a selective pressure for somatic mutations in Nrf2 or its inhibitor Keap-1, leading to constitutive Nrf2 activation. Nrf2 overexpression confers a survival advantage and is often associated with cancer cell survival. Here we review the evidence for OTA’s role as an Nrf2 inhibitor and discuss the implications of this mechanism in nephrotoxicity and carcinogenicity.
Keywords: proximal tubule; ochratoxin; oxidative; Nrf2
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MDPI and ACS Style

Limonciel, A.; Jennings, P. A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity. Toxins 2014, 6, 371-379.

AMA Style

Limonciel A, Jennings P. A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity. Toxins. 2014; 6(1):371-379.

Chicago/Turabian Style

Limonciel, Alice; Jennings, Paul. 2014. "A Review of the Evidence that Ochratoxin A Is an Nrf2 Inhibitor: Implications for Nephrotoxicity and Renal Carcinogenicity." Toxins 6, no. 1: 371-379.

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