Curcumin blocks fibrosis in anti-Thy 1 glomerulonephritis through up-regulation of heme oxygenase 1

Kidney Int. 2005 Nov;68(5):2042-9. doi: 10.1111/j.1523-1755.2005.00658.x.

Abstract

Background: Induction of heme oxygenase 1 (HO-1) has been shown to be beneficial in a variety of pathologic settings. Curcumin, a polyphenolic compound, has antifibrotic effects in lung models of fibrosis, and is known to induce HO-1 in renal tubular cells. In this study, we determined whether curcumin has antifibrotic properties in glomerular fibrosis and if these effects are mediated by induction of HO-1.

Methods: Curcumin effects on HO-1 expression in cultured mesangial cells and in glomeruli in vivo were analyzed by Northern and Western blotting. The dose-dependent effect of curcumin on glomerular fibrosis was tested in the anti-Thy 1 glomerulonephritis model. Curcumin was applied at doses of 10 to 200 mg/kg body weight by intraperitoneal injection from days 3 to 5 after induction of disease. On day 6, glomeruli were harvested and markers of fibrosis [plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta (TGF-beta), fibronectin, periodic acid-Schiff (PAS) staining] were analyzed. The effect of HO-1 inhibition was tested in a second experiment were nephritic rats were treated with curcumin (100 mg/kg body weight) or the combination of curcumin and the HO-1 inhibitor zinc protoporphyrin (100 microg/kg).

Results: Curcumin potently induced mesangial cell HO-1 expression in vitro and up-regulated glomerular HO-1 expression in nephritic animals in vivo. Curcumin treatment led to a significant, dose-dependent reduction of markers of fibrosis and proteinuria, with maximal inhibition at doses of 50 to 100 mg/kg. Beneficial effects of curcumin on markers of fibrosis and proteinuria were lost after HO-1 inhibition.

Conclusion: Curcumin has antifibrotic effects in glomerular disease, which are mediated through an induction of HO-1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Curcumin / pharmacology*
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Fibrosis
  • Glomerulonephritis / drug therapy*
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • Isoantibodies
  • Kidney Glomerulus / enzymology
  • Kidney Glomerulus / pathology
  • Male
  • Proteinuria / drug therapy
  • Proteinuria / metabolism
  • Proteinuria / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Enzyme Inhibitors
  • Isoantibodies
  • anti-Thy antibody
  • Heme Oxygenase-1
  • Curcumin