Sulfated hyaluronic acid, a potential selectin inhibitor, ameliorates experimentally induced crescentic glomerulonephritis.
OBJECTIVE
Sulfated polysaccharides are known to interfere with the binding of selectins and their ligands. Recently, we demonstrated that sulfated hyaluronic acid (SHA), a synthetic sulfated polysaccharide, showed preventive and therapeutic effects on experimental mesangial proliferative glomerulonephritis. Here we evaluated the protective potential of SHA on crescentic glomerulonephritis, using nephrotoxic serum (NTS) nephritis in Wistar-Kyoto (WKY) rats.


METHODS
Crescentic glomerulonephritis was induced by injection of NTS in WKY rats. Rats subsequently received intraperitoneal administration of SHA (0.5 or 1.5 mg/kg/day) or non-sulfated hyaluronic acid (HA) (1.5 mg/kg/day) for 14 days. The urinary protein excretion was measured, and expression of selectins, intraglomerular leukocytes and crescent formation were examined by immunohistochemistry. In addition, we examined the urinary protein excretion of SHA (1.5 mg/kg/day) administered from day 7 after the induction of crescentic glomerulonephritis.


RESULTS
The expression of P-selectin was increased in the glomerulus of crescentic glomerulonephritis. SHA reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, administration of SHA (1.5 mg/kg/day) from day 7 also reduced the urinary protein excretion on day 14 compared with that in saline and HA group.


CONCLUSIONS
Our results suggest that SHA inhibits intraglomerular infiltration of macrophages, and prevents progression of experimental crescentic glomerulonephritis. Sulfated polysaccharides might be beneficial for the treatment of crescentic glomerulonephritis.
Ogawa
Daisuke
D
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Shikata
Kenichi
K
Matsuda
Mitsuhiro
M
Akima
Kazuo
K
Iwahashi
Mitsuhiro
M
Okada
Shinichi
S
Tsuchiyama
Yoshinori
Y
Shikata
Yasushi
Y
Wada
Jun
J
Makino
Hirofumi
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005921:Glomerulonephritis; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007263:Infusions, Parenteral; D008264:Macrophages; D009393:Nephritis / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011921:Rats, Inbred WKY; D019087:Selectins / Q000187:drug effects / Q000502:physiology
D000276:Adjuvants, Immunologic; D019087:Selectins; D006820:Hyaluronic Acid