title: Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis.
abstract: BACKGROUND
  Oxidative damage and apoptosis play dominant roles in the pathogenesis of steroid-induced osteonecrosis (ON). Grape seed proanthocyanidin extract (GSPE) demonstrates antioxidant and antiapoptotic properties. Our aim was to demonstrate the effects of GSPE in preventing steroid-induced ON in rabbits.
  
  
  METHODS
  Osteonecrosis was induced by high-dose methylprednisolone (40 mg/kg). Rabbits in the preventive medicine group were treated with 100 mg/kg/day GSPE for 14 consecutive days, and the presence or absence of ON was examined histopathologically. Oxidative damage in bone tissue was assessed by immunohistochemical staining of 8-oxo-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) levels, and activities of antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (GSH-Px). Apoptosis was detected via quantitative terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate nick end labelling (TUNEL) staining and activated caspase 3 immunoblotting and activity.
  
  
  RESULTS
  GSPE significantly attenuated the changes of immunohistochemical staining of 8-OHdG, MDA levels, and antioxidant enzymes activities, which were caused by methylprednisolone administration. Quantitative TUNEL and caspase 3 assay showed lower apoptosis with GSPE application. Simultaneously, GSPE reduced the incidence of steroid-induced ON in an established rabbit model to 17.6 %, compared with 87.5 % in the steroid-only group.
  
  
  CONCLUSIONS
  These results reveal that GSPE treatment could inhibit oxidative damage and apoptosis to exert beneficial effects on reducing the incidence of steroid-induced ON in rabbit models.
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, People's Republic of China.
authors.forename: Qichun
authors.initials: Q
authors.lastname: Song
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Shi
authors.forename: Wenchao
authors.initials: W
authors.lastname: Bi
authors.forename: Ruiyu
authors.initials: R
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D005938:Glucocorticoids; D056604:Grape Seed Extract / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone; D010020:Osteonecrosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D005938:Glucocorticoids; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D044945:Proanthocyanidins; D008775:Methylprednisolone