The effects of thymoquinone on steroid-induced femoral head osteonecrosis: An experimental study in rats
Mustafa Fatih Dasci1, Elif Yaprak Sarac2, Asiye Gok Yurttas3, Tolgahan Atci4, Muhammed Uslu1, Abdurrahman Acar1, Mehmet Akif Gulec1, Ender Alagoz1
1Department of Orthopedics and Traumatology, University of Health Sciences, Bağcılar Training and Research Hospital, Istanbul, Türkiye
2Molecular Biology and Genetics and Biotechnology, Istanbul Technical University, Istanbul, Türkiye
3Department of Biochemistry, Istanbul Health and Technology University Faculty of Pharmacy, Istanbul, Türkiye
4Department of Orthopedics and Traumatology, Letoon Hospital, Muğla, Türkiye
Keywords: Lipopolysaccharide, methylprednisolone, osteonecrosis of femoral head, thymoquinone.
Objectives: In this study, we aimed to evaluate the antioxidant, anti-apoptotic, osteoblastic and hypolipidemic effects of thymoquinone (TQ) treatment on the steroid-induced osteonecrosis of femoral head (ONFH) model in rats.
Materials and methods: A total of 24 rats were randomly divided into four groups: the control group administered saline; the TQ group administered 10 mg/kg/day TQ orally; lipopolysaccharide/methylprednisolone (LPS/MPS) group administered 20 µg/kg intraperitoneally LPS and 40 mg/kg intramuscularly MPS to establish ONFH model; and the LPS/ MPS+TQ group administered both LPS/MPS and, then, TQ once daily for four weeks. All rats were sacrificed after intracardiac blood collection and their right femurs were removed.
Results: Micro-computed tomography showed a higher bone mineral density and lower porosity, Tr. Sp and Tr. Sep data were detected in the LPS/MPS+TQ group. In histopathology, osteonecrosis increased significantly in the LPS/MPS group and osteonecrosis decreased in the LPS/MPS+TQ group compared to the LPS/MPS group (p=0.0077). Histomorphometric examination revealed that the percentage of BV/TV in the LPS/MPS group was significantly lower compared to control and other groups (p<0.01 and p<0.05, respectively), while it reached normal rates in the LPS/MPS+TQ group. Immunohistochemically, antioxidant, anti-apoptotic, and angiogenesis indicators (8-hydroxy-20- deoxyguanosine [8-OHdG], malondialdehyde [MDA], B-cell lymphoma [Bcl-2], caspase-3, vascular endothelial growth factor [VEGF]) were significantly improved in tissue and serum with TQ. Furthermore, TQ significantly reduced low- and high-density lipoprotein cholesterol ratio and carboxy-terminal type 1 collagen crosslink (CTX) in serum.
Conclusion: Vascular and hematopoietic cell damages that occur due to steroid-induced deoxyribonucleic acid (DNA) oxidative and lipid peroxidative damages in an ONFH model can be successfully ameliorated by TQ administration. This antioxidant and anti-apoptotic effects of TQ may be a promising treatment option for early stage of osteonecrosis.
Citation: Dasci MF, Yaprak Sarac E, Gok Yurttas A, Atci T, Uslu M, Acar A, et al. The effects of thymoquinone on steroid-induced femoral head osteonecrosis: An experimental study in rats. Jt Dis Relat Surg 2022;33(3):553-566.
The ethics committee approval was received from Experimental/Animal Research Center in University of Health Sciences, Istanbul Bagcilar Training and Research Hospital. (Meeting date: 05.03.2019, Meeting No: 2019/57, Project No: 2019-03). All animal experiments were conducted in compliance with the “Guide for the Care and Use of Laboratory Animals” published by the US National Institutes of Health (revised, 1985).
Data Sharing Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Writing, editing, analysis: M.F.D.; Writing, data collection, statistics: E.Y.S.; Data collection, analysis: A.G.Y.; Data collection, proofreading, editing: T.A.; Analysis, statistics, writing, editing: M.U.; Data collection, analysis, statistics: A.A.; Supervision, proofreading: M.A.G.; Supervision, proofreading, editing: E.A.; All authors contributed to the study conception and design. All authors read and approved the final manuscript.
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
The authors received no financial support for the research and/or authorship of this article.
We would like to thank the Bagcilar Training and Research Hospital Experimental Research and Skill Development Center for their kind contributions and support. We also appreciate the assistance of Göker Külüslü from Istanbul Technical University Biomedical Engineering Department, for him help during the Micro CT scan analyses.