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


CONCLUSIONS
Curcumin has antifibrotic effects in glomerular disease, which are mediated through an induction of HO-1.
Gaedeke
Jens
J
Fibrosis Research Laboratory, University of Utah, Salt Lake City, 84108, USA.
Noble
Nancy A
NA
Border
Wayne A
WA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005355:Fibrosis; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007518:Isoantibodies; D007678:Kidney Glomerulus / Q000201:enzymology / Q000473:pathology; D008297:Male; D011507:Proteinuria / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007518:Isoantibodies; C035678:anti-Thy antibody; D051547:Heme Oxygenase-1; D003474:Curcumin