Lansoprazole halts contrast induced nephropathy through activation of Nrf2 pathway in rats

Chem Biol Interact. 2017 May 25:270:33-40. doi: 10.1016/j.cbi.2017.04.010. Epub 2017 Apr 13.

Abstract

Contrast-induced nephropathy (CIN) is an important cause of acute kidney injury characterized by significant mortality and morbidity. To date, there is no successful protective regimen for CIN especially in poor kidney function patients. Lansoprazole has been shown to exert antioxidant action through induction of nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. The aim of the present study is to investigate the potential of lansoprazole to activate Nrf2 pathway in the kidney and consequently to protect against oxidative stress induced by iodinated contrast media. Lansoprazole, at a dose of 100 mg/kg, showed a significant induction of Nrf2 mRNA after 3 h. Administration of contrast media induced significant increase in serum creatinine and blood urea nitrogen, histological deterioration, and reduction in total antioxidant capacity. Moreover, it instigated the defensive Nrf2 gene expression and immunoreactivity. In addition, there were overexpression of HO-1, caspase 3, p53 and IL6 genes and downregulation of Bcl2 gene. Pre-treatment with lansoprazole (100 mg/kg) ameliorated the nephrotoxicity parameters and oxidative stress, improved histological lesions, and hijacked apoptotic and inflammatory markers that were provoked by contrast media. In conclusion, lansoprazole attenuates experimental CIN which might be due to activation of Nrf2 antioxidant defence pathway. These findings highlight the potential benefit of incorporating lansoprazole in the protective regimen against CIN especially for susceptible patients.

Keywords: Contrast induced nephropathy; Lansoprazole; Nrf2; Oxidative stress.

MeSH terms

  • Administration, Oral
  • Animals
  • Contrast Media / toxicity
  • Fluorescent Antibody Technique
  • Heme Oxygenase-1 / metabolism*
  • Kidney / drug effects*
  • Kidney / pathology
  • Lansoprazole / pharmacology*
  • Lansoprazole / therapeutic use*
  • Male
  • NF-E2-Related Factor 2 / drug effects*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Nephritis / chemically induced
  • Nephritis / drug therapy*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Up-Regulation / drug effects

Substances

  • Contrast Media
  • NF-E2-Related Factor 2
  • Lansoprazole
  • Heme Oxygenase-1