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- Title
Curcumin blocks fibrosis in anti-Thy 1 glomerulonephritis through up-regulation of heme oxygenase 1.
- Authors
Gaedeke, Jens; Noble, Nancy A.; Border, Wayne A.
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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.<bold>Conclusion: </bold>Curcumin has antifibrotic effects in glomerular disease, which are mediated through an induction of HO-1.
- Subjects
HEME oxygenase; RENAL artery; GLOMERULONEPHRITIS; IMMUNE complex diseases; KIDNEY glomerulus diseases; FIBROSIS
- Publication
Kidney International, 2005, Vol 68, Issue 5, p2042
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1111/j.1523-1755.2005.00658.x