title: Sulfated hyaluronic acid, a potential selectin inhibitor, ameliorates experimentally induced crescentic glomerulonephritis.
abstract: 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.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ogawa
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Akima
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Iwahashi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsuchiyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shikata
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D019087:Selectins; D006820:Hyaluronic Acid