Oxidative stress by glutathione depletion induces osteonecrosis in rats.
OBJECTIVE
We recently implicated in vivo oxidative stress in the development of osteonecrosis in a steroid-induced osteonecrosis model in the domestic rabbit. In the present experiment we devised a new non-traumatic model using the rat to investigate the relationship between oxidative stress and the development of osteonecrosis.


METHODS
Seven 24-week-old male Wistar rats were subcutaneously injected with the pro-oxidant buthionine sulphoximine (BSO) 500 mg/kg for 14 consecutive days (group B) and eight rats received injections of vehicle (physiological saline; group N). The rats in both groups were killed after 14 days, and their bilateral femurs were examined histopathologically. Blood levels of reduced glutathione (GSH), total cholesterol (T-cho) and triglycerides (TG) were also determined.


RESULTS
GSH was significantly decreased in group B compared with group N (P < 0.01). No significant differences were found in T-cho or TG. Osteonecrosis was not detected in any animal in group N in contrast to five of seven animals in group B (P < 0.05).


CONCLUSIONS
BSO is an inducer of oxidative stress, in particular interfering with the synthesis of GSH in vivo. In the present study, GSH levels were markedly reduced by BSO, whereas neither T-cho nor TG was significantly changed. The high rate of osteonecrosis noted in group B suggests that oxidative stress alone may be sufficient to promote the development of osteonecrosis at certain sites.
Ichiseki
T
T
Department of Orthopaedic Surgery, Kanazawa Medical University, Ishikawa, Japan. tsy-ichi@kanazawa-med.ac.jp
Ueda
Y
Y
Katsuda
S
S
Kitamura
K
K
Kaneuji
A
A
Matsumoto
T
T
D000818:Animals; D019328:Buthionine Sulfoximine; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005260:Female; D005978:Glutathione / Q000097:blood / Q000172:deficiency*; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D019328:Buthionine Sulfoximine; D005978:Glutathione