Abstract
Introduction
The mechanism for development of corticosteroid-induced osteonecrosis of the femoral head remains to be understood. Elucidation of the mechanism and the establishment of preventive methods have been critical issues. To establish a clinical method for prevention of corticosteroid-induced osteonecrosis, we have examined the suppressive effect of reduced glutathione (GSH) in a corticosteroid-induced rabbit model.
Methods
Female Japanese white rabbits were separated into five groups: Group S4, a single intramuscular 4 mg/kg methyl prednisolone acetate (MPSL) administration in the gluteus; Group G4, administration of a 5 mg/kg regular dose GSH for 5 consecutive days starting on the day of a single 4 mg/kg MPSL administration; Group S20, a single intramuscular administration of 20 mg/kg MPSL in the gluteus; Group G20, administrations of 5 mg/kg GSH for 5 consecutive days starting on the day of a single 20 mg/kg MPSL administration; and Group N, control group with no treatment. All rabbits were sacrificed 14 days after MPSL administration. Histopathological analyses were performed by hematoxylin-eosin staining. Immunohistological analyses were performed using anti-lectinlike oxidized LDL reseptor-1 antibody (anti-LOX-1 antibody).
Results
Osteonecrosis occurred in 70% of the animals in Group S4, whereas, no osteonecrosis was observed in Group G4, showing a significant suppression. Osteonecrosis was observed in 90% of the animals in Group S20, and it was significantly suppressed in Group G20, with only 30% of the animals affected. The expression of LOX-1 was significantly elevated in Groups S4 and S20. In Group N, no osteonecrosis was observed in all cases, while the expression of LOX-1 was only marginally detected.
Conclusion
Abnormal expression of LOX-1 which was examined in the present study is used as an indicator of tissue hyperoxidation. GSH is known to be an enzyme which protect tissues and the vascular endothelium. In the present study, significant suppression of osteonecrosis was observed in Groups G4 and G20 which received GSH administrations, in which osteonecrosis occurred in 0 and 30%, respectively. In addition, LOX-1 expression was also reduced. These results showed that GSH at the regular dose suppressed oxidative stress and development of osteonecrosis, suggesting an effective clinical application of GSH.
