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  • Title: Beneficial effect of grape seed proanthocyanidin extract in rabbits with steroid-induced osteonecrosis via protecting against oxidative stress and apoptosis.
    Author: Song Q, Shi Z, Bi W, Liu R, Zhang C, Wang K, Dang X.
    Journal: J Orthop Sci; 2015 Jan; 20(1):196-204. PubMed ID: 25287583.
    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. CONCLUSION: 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.
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