Therapeutic effects of ulinastatin on experimental crescentic glomerulonephritis in rats.
Ulinastatin is a potent protease inhibitor purified from the human urine that has been used clinically to treat acute pancreatitis and circulatory shock. In the current study, we evaluated the therapeutic effects of Ulinastatin in a rat model of crescentic glomerulonephritis (CrGN) and investigated its putative mechanisms. Wistar-Kyoto rats were injected with nephrotoxic serum and received daily intraperitoneal injection of Ulinastatin. Ulinastatin treatment significantly reduced proteinuria and glomerular crescentic formation. Moreover, glomerular infiltration of neutrophils and ED1+ cells (monocytes/macrophages) was significantly suppressed by Ulinastatin. In contrast, the glomerular deposition of heterologous (rabbit) and autologous (rat) antibodies was not changed. Neither serum complement activation nor the anti-rabbit immune response was affected by Ulinastatin administration. Our results suggest that Ulinastatin has preventive effects on rat experimental CrGN, mediated at least in part by inhibiting intraglomerular infiltration of inflammatory cells.
Koizumi
R
R
Third Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Kanai
H
H
Maezawa
A
A
Kanda
T
T
Nojima
Y
Y
Naruse
T
T
D000818:Animals; D003165:Complement System Proteins / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005921:Glomerulonephritis / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011507:Proteinuria / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY
D006023:Glycoproteins; D011480:Protease Inhibitors; D003165:Complement System Proteins; D003404:Creatinine; C028665:urinastatin