The timing and extent of intraosseous hypoxia in the oxidative stress-induced rat osteonecrosis model

Toru Ichiseki, Ayumi Kaneuji, Seiji Kaneko, Syusuke Ueda, Yoshimichi Ueda, Hideto Yonekura, Kiyokazu Fukui, Tadami Matsumoto

Department of Biochemistry, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Department of Orthopaedic Surgery, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.

DOI: 10.4236/abb.2013.48107                

Abstract

Using a rat oxidative stress-induced femoral head osteonecrosis model, we determined the presence/ absence and timing of the generation of hypoxia in the femoral head. DL-Buthionine-(S,R)-sulfoximine (BSO) 500 mg/kg was administered intraperitoneally to male Wistar rats. The rats were killed at 1, 3, 6, 12 hours, and 1, 3, 5 days after BSO administration, and the bilateral femora were removed. A group not administered BSO (control group) was also studied (each group n = 5). In the femoral heads of each group, the expression of hypoxia-inducible factor-1 alpha (HIF-1α) as an index of hypoxia was confirmed by the Western blot method, and quantified using analytical software. In the femoral head increased HIF-1α expression was found in all groups from 1 hour after BSO administration (p < 0.05). In particular, in all specimens of the group 3 hours after BSO administration the most intense expression of HIF-1α amounting to about 13-fold of that of control group was noted (p < 0.001). The present results suggested that in the extremely short period of 3 hours after BSO administration hypoxia severe enough to cause osteonecrosis was induced by oxidative stress in the rat femoral head.

Keywords

Osteonecrosis; Oxidative Stress; Buthionine Sulfoximine; Hypoxia-Inducible Factor-1α

Conflicts of Interest

The authors declare no conflicts of interest.

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