5-ALA/SFC enhances HO-1 expression through the MAPK/Nrf2 antioxidant pathway and attenuates murine tubular epithelial cell apoptosis

FEBS Open Bio. 2019 Nov;9(11):1928-1938. doi: 10.1002/2211-5463.12729. Epub 2019 Sep 30.

Abstract

Cyclosporin A (CsA) is a common immunosuppressant, but its use is limited as it can cause chronic kidney injury. Oxidative stress and apoptosis play a key role in CsA-induced nephrotoxicity. This study investigated the protective effect of 5-aminolevulinic acid and iron (5-ALA/SFC) on CsA-induced injury in murine proximal tubular epithelial cells (mProx24). 5-ALA/SFC significantly inhibited apoptosis in CsA-treated mProx24 cells with increases in heme oxygenase (HO)-1, nuclear factor E2-related factor 2 (Nrf2), and p38, and Erk-1/2 phosphorylation. Moreover, 5-ALA/SFC suppressed production of reactive oxygen species in CsA-exposed cells and inhibition of HO-1 suppressed the protective effects of 5-ALA/SFC. In summary, 5-ALA/SFC may have potential for development into a treatment for the anti-nephrotoxic/apoptotic effects of CsA.

Keywords: 5-aminolevulinic acid; Cyclosporine A; apoptosis; heme oxygenase-1; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminolevulinic Acid
  • Animals
  • Antioxidants / metabolism*
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Citric Acid
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Ferrous Compounds / pharmacology*
  • Heme Oxygenase-1 / biosynthesis*
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Levulinic Acids / pharmacology*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism

Substances

  • Antioxidants
  • Ferrous Compounds
  • Levulinic Acids
  • NF-E2-Related Factor 2
  • Citric Acid
  • ferrous citrate
  • Heme Oxygenase-1
  • Mitogen-Activated Protein Kinases