Beneficial effect of neutrophil elastase inhibitor on anti-Thy1.1 nephritis in rats.
BACKGROUND
Neutrophil elastase, one of the proteinases released by neutrophils, plays an important role at the sites of inflammation and was reported to be involved in the pathogenesis of glomerulonephritis. Sivelestat is a selective neutrophil elastase inhibitor used for acute lung injury associated with systemic inflammatory response syndrome. There have been few reports on the effects of sivelestat on renal disease.


METHODS
In male Wistar rats, anti-Thy1.1 nephritis was induced by the injection of anti-Thy1.1 antibody. The rats were divided into four groups: nephritic rats treated with low- (group A) and high-dose sivelestat (group B), those not treated with sivelestat (group C) and control rats (group D). Urine samples were obtained every day during the experiment. The rats were killed on day 6 in order to obtain the blood plasma and kidneys. Measurement of urine protein levels, blood biochemical values and histological examination of the kidneys were carried out.


RESULTS
Increased levels of proteinuria were observed in the nephritic rats (groups A, B and C) compared with group D. The proteinuria level was significantly suppressed by sivelestat in groups A and B in a dose-dependent fashion compared with group C. The light microscopy revealed an increased glomerular cell count in group C, which was significantly suppressed in group B. In the electron microscopic study, sivelestat suppressed the fusion of epithelial foot process, especially in group B.


CONCLUSIONS
Neutrophil elastase is suggested to be involved in the development of anti-Thy1.1 nephritis, and the neutrophil elastase inhibitor sivelestat reduces the tissue injury of anti-Thy1.1 nephritis in rats.
Kumasaka
Ryuichiro
R
The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan. rkuma-cc@umin.ac.jp
Nakamura
Norio
N
Fujita
Takeshi
T
Murakami
Reiichi
R
Shimada
Michiko
M
Osawa
Hiroshi
H
Yamabe
Hideaki
H
Okumura
Ken
K
D000818:Animals; D004195:Disease Models, Animal; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009393:Nephritis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D018800:Thy-1 Antigens / Q000276:immunology; D016896:Treatment Outcome
D053491:Proteinase Inhibitory Proteins, Secretory; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D018800:Thy-1 Antigens; C069195:sivelestat; D005998:Glycine