Bezafibrate suppresses rat antiglomerular basement membrane crescentic glomerulonephritis.
BACKGROUND
The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model.


METHODS
The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells.


RESULTS
Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats.


CONCLUSIONS
BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.
Saga
Daisuke
D
Division of Clinical Nephrology and Rheumatology, Department of Laboratory Medicine Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, Japan.
Sakatsume
Minoru
M
Ogawa
Asa
A
Tsubata
Yutaka
Y
Kaneko
Yoshikatsu
Y
Kuroda
Takeshi
T
Sato
Fuminori
F
Ajiro
Junya
J
Kondo
Daisuke
D
Miida
Takashi
T
Narita
Ichiei
I
Gejyo
Fumitake
F
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001485:Basement Membrane / Q000276:immunology; D001629:Bezafibrate / Q000378:metabolism / Q000494:pharmacology*; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors
D000906:Antibodies; D047493:PPAR alpha; D001629:Bezafibrate