Oxidative stress by glutathione depletion induces osteonecrosis in rats.

Abstract

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. 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. 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). 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.