Porous Se@SiO2 nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

Guoying Deng; Chenyun Dai; Jinyuan Chen; Anqi Ji; Jingpeng Zhao; Yue Zhai; Yingjie Kang; Xijian Liu; Yin Wang; Qiugen Wang

doi:10.2147/IJN.S159776

Porous Se@SiO₂ nanocomposites protect the femoral head from methylprednisolone-induced osteonecrosis

Int J Nanomedicine. 2018 Mar 22:13:1809-1818. doi: 10.2147/IJN.S159776. eCollection 2018.

Authors

Guoying Deng^#¹, Chenyun Dai^#², Jinyuan Chen¹, Anqi Ji¹, Jingpeng Zhao¹, Yue Zhai¹, Yingjie Kang³, Xijian Liu⁴, Yin Wang⁵, Qiugen Wang¹

Affiliations

¹ Trauma Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Institute of Translation Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Department of Radiology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China.
⁵ Ultrasound Department of Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

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@SiO₂ 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-1β and TNF-α. And oxidative stress species (ROS) index like superoxide dismutase (SOD) and glutathione (GSH) were tested. Then, the protection effects of Se@SiO₂ 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@SiO₂ 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@SiO₂ did not affect the reduced wet-to-dry weight ratio of MPS. Se@SiO₂ also did not impair the effect of MPS on the reduction of inflammatory factors IL-1β and TNF-α, and on the alleviation of structural destruction. Furthermore, micro CT and histologic analysis confirmed that Se@SiO₂ significantly alleviate MPS-induced destruction of femoral head. Moreover, compared with MPS group, Se@SiO₂ could increase collagen II and aggrecan, and reduce the IL-1β level in the cartilage of femoral head. In addition, the biosafety of Se@SiO₂ in vitro and in vivo were supported by cell proliferation assay and histologic analysis of main organs from rat models.

Conclusion: Se@SiO₂ 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: ARDS; ROS damage; methylprednisolone; osteonecrosis of femoral head; porous Se@SiO2 nanocomposites.

MeSH terms

Animals
Cell Line
Disease Models, Animal
Femur Head Necrosis / chemically induced*
Femur Head Necrosis / pathology
Femur Head Necrosis / therapy*
Male
Methylprednisolone / adverse effects*
Nanocomposites / chemistry
Nanocomposites / therapeutic use*
Nanocomposites / ultrastructure
Porosity
Protective Agents / pharmacology
Protective Agents / therapeutic use*
Rats, Sprague-Dawley
Respiratory Distress Syndrome / drug therapy
Selenium / therapeutic use*
Silicon Dioxide / pharmacology
Silicon Dioxide / therapeutic use*
X-Ray Microtomography

Substances

Protective Agents
Silicon Dioxide
Selenium
Methylprednisolone