K. Mosley et al., HEME OXYGENASE IS INDUCED IN NEPHROTOXIC NEPHRITIS AND HEMIN, A STIMULATOR OF HEME OXYGENASE SYNTHESIS, AMELIORATES DISEASE, Kidney international, 53(3), 1998, pp. 672-678
Heme oxygenase (HO) catalyses degradation of heme to biliverdin, iron
and carbon monoxide (CO). Two isoforms exist, a constitutive form and
an inducible form (HO-1). Induction of HO-1 may have protective effect
s in inflammation. We studied heterologous (HNTN) and accelerated (ANT
N) nephrotoxic nephritis in Lewis rats. Hemin. an inducer of HO-1. (30
mu mol/kg) was administered 18 hours before induction of nephritis an
d 72 hours later in ANTN. HO-1 was not detected immunohistochemically
in normal glomeruli but was present in HNTN and ANTN in cells with the
morphology of macrophages. HO-1 induction was confirmed by RT-PCR. In
normal rats hemin induced glomerular HO-1 mRNA at 18 hours. In HNTN h
emin markedly reduced proteinuria at 24 hours (10 +/- 4 mg/24 hr; cont
rol 54 +/- 16; P < 0.05), neutrophil infiltration at two hours (29.8 /- 1.8 vs. 22.3 +/- 1.5 neutrophils/glomerulus, P < 0.05), and glomeru
lar macrophage number at two hours (2.1 +/- 0.1 vs. 3.1 +/- 0.4 cells/
glomerulus, P < 0.05). In ANTN proteinuria was reduced al dal; 1 and d
ay 4 (36 +/- 11 vs. 60 +/- 15 and 35 +/- 7 vs. 86 +/- 9 mg protein/24
hr, respectively, P < 0.001), glomerular thrombi were reduced by hemin
at day 1 and 4 (1.5 +/- 2.7 vs. 3.7 +/- 0.2 and 1.3 +/- 0.01 vs. 2.9
+/- 0.02, respectively. P < 0.001) and glomerular macrophage infiltrat
ion was reduced on day 4 (11.2 +/- 0.8 cells/glom; control 15.9 +/- 0.
8, P < 0.01). Possible mechanisms by which HO-1 ameliorates disease in
clude anti-complement or anti-oxidant effects of bilirubin and vasodil
ator and anti-platelet effects of carbon monoxide.