Nrf2 activators as potential modulators of injury in human kidney cells

Amandla Atilano-Roque1, Xia Wen2, Lauren M Aleksunes2

  • 1Department of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of Colorado, 12850 E. Montview Blvd, Aurora, CO 80045, United States.

Toxicology Reports
|September 30, 2017
PubMed

Insights

Nrf2 activators like sulforaphane may protect kidney cells from cisplatin damage. These compounds enhanced cell viability and antioxidant gene expression, suggesting potential therapeutic benefits.

Area of Science:

  • Nephrology
  • Pharmacology
  • Molecular Biology

Background:

  • Cisplatin is a vital chemotherapy drug but causes significant kidney toxicity.
  • Nuclear factor (erythroid-derived-2)-like 2 (Nrf2) plays a crucial role in cellular defense mechanisms against oxidative stress and kidney protection.

Purpose of the Study:

  • To investigate the protective potential of Nrf2 activators (oltipraz, sulforaphane, oleanolic acid) against cisplatin-induced kidney cell injury.
  • To compare the efficacy of these Nrf2 activators in mitigating cisplatin nephrotoxicity.

Main Methods:

  • Human proximal tubule cells (hPTC) and HEK293 cells were treated with cisplatin.
  • Cells were co-exposed to cisplatin and Nrf2 activators (oltipraz, sulforaphane, oleanolic acid) with varied timing (pre- and delayed-treatment).
  • Cell viability assays and analysis of antioxidant gene expression (GCLC, NQO1) were performed.

Main Results:

  • Nrf2 activator treatment significantly enhanced cell viability in the presence of cisplatin.
  • The timing of Nrf2 activator exposure (pre- vs. delayed) influenced protective effects.
  • Sulforaphane and oltipraz notably increased the expression of antioxidant genes GCLC and NQO1.

Conclusions:

  • Nrf2 activators demonstrate potential for protecting human kidney cells from cisplatin-induced toxicity.
  • Strategic administration timing of Nrf2 activators may optimize nephroprotective outcomes.
  • Further research into Nrf2 activator therapy could offer novel strategies for managing cisplatin nephrotoxicity.

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