RESUMEN
OBJECTIVE: To investigate the relationship between transient oxidative stress and the development of osteonecrosis in a rat model. METHODS: A total of 160 male Wistar rats (24 weeks old) were injected only once with the pro-oxidant DL-buthionine-(S,R)-sulfoximine (BSO) (500 mg/kg given intraperitoneally) and were killed 12 hours (group A), 1 day (group B), 3 days (group C), 4 days (group D), 5 days (group E), 7 days (group F), or 14 days (group G) after administration (n = 20 per group). Twenty untreated rats were used as a control group (group N). Femurs were examined histopathologically for the presence of osteonecrosis, and reduced glutathione (GSH) in liver tissue was measured as an index of oxidative stress. RESULTS: GSH decreased rapidly after BSO administration. Significant decreases were noted in groups A and B as compared to group N (P < 0.0001 and P = 0.0007, respectively), confirming the development of transient extreme oxidative stress soon after BSO administration. The histopathologic study revealed osteonecrosis in 10% of the rats in group E, 35% of the rats in group F, and 40% of the rats in group G. CONCLUSION: Transient extreme oxidative stress was confirmed to induce osteonecrosis in this model. Since preparation of this model is extremely simple and because rats are well suited to genetic studies, this model may be of use in elucidating the pathophysiology of femoral head osteonecrosis in future studies.
Asunto(s)
Osteonecrosis/etiología , Estrés Oxidativo/fisiología , Animales , Butionina Sulfoximina , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Osteonecrosis/metabolismo , Osteonecrosis/patología , Ratas , Ratas WistarRESUMEN
BACKGROUND: We focused on vitamins with marked antioxidant potency to see whether their use might prevent the development of steroid-induced osteonecrosis. METHODS: Fifteen Japanese white rabbits weighing about 3.5 kg were injected once into the right gluteal muscle with methylpred-nisolone (MPSL) 40 mg/kg (S group). In addition, 10 other rabbits received consecutive daily intravenous injections of vitamin E 50 mg/kg, starting from the day of MPSL administration (E group). All animals were killed 2 weeks after MPSL administration, and femurs were extracted and stained with H&E. Blood levels of reduced glutathione (GSH) were also measured. RESULTS: In the S group the osteonecrosis development rate was 93%, in contrast to 0% in the E group (P < 0.01). Also, GSH levels in the S group abruptly decreased from the first day after MPSL administration, whereas in the E group, the decline in GSH levels was significantly suppressed on days 1 and 3 after MPSL administration (P< 0.05). CONCLUSIONS: Vitamin E administration significantly inhibited steroid-induced oxidative stress. The results of this study suggest that the administration of vitamin E may be a novel and simple method to prevent the development of steroid-induced osteonecrosis.