Heme oxygenase-1 inducer hemin attenuates the progression of remnant kidney model.
OBJECTIVE
Heme oxygenase-1 (HO-1) has been shown to protect against fibrotic proliferation and apoptosis in several models of renal damage. The purpose of this study was to evaluate the impact of a treatment with the HO-1 inducer hemin on the progression of chronic kidney disease in nephrectomized rats versus the AT1 receptor antagonist losartan.


METHODS
The rats underwent 5/6 renal ablation and after the procedure received either losartan (20 mg/kg/day; n = 9), hemin (50 mg/kg/twice a week; n = 8) or vehicle (n = 8) over a 12-week period. At week 12, blood pressure was measured, urine, blood and remnant kidney were collected for biochemical (proteinuria, urea, creatinine) and histopathological (degrees of glomerulosclerosis and tubular atrophy) analysis. The expressions of HO-1, bone morphogenic protein 7 (BMP-7) and TGF-beta were assessed by immunochemistry, and the level of the apoptosis marker protein caspase-3 by Western blot, on the remnant kidney.


RESULTS
Hemin significantly reduced blood pressure, proteinuria, inhibited the expression of TGF-beta and caspase-3 protein and increased BMP-7 expression protein. Hemin-treated rats had lower glomerulosclerosis and tubular atrophy indexes than controls.


CONCLUSIONS
Hemin treatment attenuates the progression of chronic kidney disease and appears more efficient than losartan in our rat model hypothetically because of the impact of hemin on the renal expression of BMP-7.
Desbuards
Nicolas
N
LABPART, EA 3852, IFR135, Université François Rabelais, FR-37032 Tours, France.
Hyvelin
Jean-Marc
JM
Machet
Marie-Christine
MC
Eder
Véronique
V
Garrigue
Marie-Ange
MA
Halimi
Jean-Michel
JM
Antier
Daniel
D
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis; D053148:Caspase 3 / Q000096:biosynthesis; D018450:Disease Progression; D004790:Enzyme Induction; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D005921:Glomerulonephritis / Q000209:etiology / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis
D055419:Bone Morphogenetic Protein 7; D053773:Transforming Growth Factor beta1; D006427:Hemin; D051547:Heme Oxygenase-1; D053148:Caspase 3; D019808:Losartan