title: Edaravone, a novel free radical scavenger, prevents steroid-induced osteonecrosis in rabbits.
abstract: OBJECTIVE
  To investigate the efficacy of edaravone, a novel free radical scavenger, on preventing steroid-induced osteonecrosis (ON) in a rabbit model.
  
  
  METHODS
  Thirty-six New Zealand white rabbits were divided into control (C; n = 6), steroid-administered (S; n = 15) and edaravone-administered groups (E; n = 15) after receiving an established protocol of steroid-induced ON. Before and after steroid administration, plasma levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were measured for oxidative stress. Two weeks later bilateral proximal femurs were dissected for micro-CT-based micro-angiography, and the presence or absence of ON and intravascular thrombi were examined histopathologically. Immunohistochemical examination of oxidative injury in bone tissue was conducted using the anti-8-hydoxy-2'-deoxyguanosine and anti-malondialdehyde mAbs.
  
  
  RESULTS
  The incidence of ON in the E group (20%) was significantly lower than in the S group (73%). Three to five days after steroid administration, the plasma GSH level was significantly higher and LPO level was significantly lower in the E group than the S group. Compared with the S group, there were significantly more small-sized perfusion vessels and fewer large-sized dilated vessels in the E group. Thrombosis incidence was significantly lower in the E group than the S group. Intraosseous vessels and haematopoietic cells that sustained oxidative injury were significantly fewer in the E group than the S group.
  
  
  CONCLUSIONS
  Edaravone exerted beneficial effects on reducing incidence of steroid-induced ON by suppressing the accumulation of lipid peroxidative products and oxidative DNA damage in endothelial cells and haematopoietic cells.
authors.affiliation: Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Guang-Yi
authors.initials: GY
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
authors.forename: Tak S
authors.initials: TS
authors.lastname: Cheng
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Yin
authors.forename: Chang-Qing
authors.initials: CQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000009:adverse effects*; D005978:Glutathione / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008775:Methylprednisolone / Q000009:adverse effects*; D010020:Osteonecrosis / Q000139:chemically induced / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D016166:Free Radical Scavengers; D005938:Glucocorticoids; D005978:Glutathione; D000077553:Edaravone; D000983:Antipyrine; D008775:Methylprednisolone