Nordihydroguaiaretic acid induces Nrf2 nuclear translocation in vivo and attenuates renal damage and apoptosis in the ischemia and reperfusion model

Phytomedicine. 2013 Jul 15;20(10):775-9. doi: 10.1016/j.phymed.2013.03.020. Epub 2013 Apr 30.

Abstract

It has been shown that the pretreatment with nordihydroguaiaretic acid (NDGA), a lignan with direct and indirect antioxidant properties, protects against the ischemia-reperfusion (I/R)-induced renal oxidant damage. Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC-PK1 cells in culture, it is unknown if NDGA may induce Nrf2 translocation in vivo. In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni-nephrectomy (U-NX) or I/R injury. Four groups of male Wistar rats were used: U-NX, NDGA, I/R, and I/R+NDGA. NDGA was injected i.p. (10mg/kg/day) starting 48 h before I/R. Kidney samples were obtained at 3 h of reperfusion after to measure Nrf2 translocation. Additional groups of rats were studied at 24 h of reperfusion to measure histological damage and apoptosis. NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis. It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I/R.

Keywords: Antioxidant; Ischemia and reperfusion; Nrf2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Apoptosis / drug effects*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Male
  • Masoprocol / pharmacology*
  • Masoprocol / therapeutic use
  • NF-E2-Related Factor 2 / metabolism*
  • Nuclear Localization Signals / biosynthesis*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Nuclear Localization Signals
  • Masoprocol