Porous Se@Si[O.sub.2] nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

Background: Methylprednisolone (MPS) is an important drug used in therapy of many diseases. However, osteonecrosis of the femoral head is a serious damage in the MPS treatment. Thus, it is imperative to develop new drugs to prevent the serious side effect of MPS. Methods: The potential interferences Se@Si[O.sub.2] nanocomposites may have to the therapeutic effect of methylprednisolone (MPS) were evaluated by classical therapeutic effect index of acute respiratory distress syndrome (ARDS), such as wet-to-dry weight ratio, inflammatory factors IL-1 [beta] and TNF-[alpha]. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@Si[O.sub.2] have in osteonecrosis of the femoral head (ONFH) were evaluated by micro CT, histologic analysis and Western-blot analysis. Results: In the present study, we found that in the rat model of ARDS, Se@Si[O.sub.2] nanocomposites induced SOD and GSH indirectly to reduce ROS damage. The wet-to-dry weight ratio of lung was significantly decreased after MPS treatment compared with the control group, whereas the Se@Si[O.sub.2] did not affect the reduced wet-to-dry weight ratio of MPS. Se@Si[O.sub.2] also did not impair the effect of MPS on the reduction of inflammatory factors IL-1[beta] and TNF-[alpha], and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@Si[O.sub.2] significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@Si[O.sub.2] could increase collagen II and aggrecan, and reduce the IL-1 [beta] level in the cartilage of femoral head. In addition, the biosafety of Se@Si[O.sub.2] in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models. Conclusion: Se@Si[O.sub.2] nanocomposites have a protective effect in MPS-induced ONFH without influence on the therapeutic activity of MPS, suggesting the potential as effective drugs to avoid ONFH in MPS therapy. Keywords: porous Se@Si[O.sub.2] nanocomposites, methylprednisolone, osteonecrosis of femoral head, ROS damage, ARDS