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Effects of sodium ferulate on preventing steroid-induced femoral head osteonecrosis in rabbits

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Abstract

The aim of this study is to investigate the effects and possible mechanisms of sodium ferulate (SF) on anti-apoptosis in steroid-induced femoral head osteonecrosis in rabbits. Japanese white rabbits were randomly divided into three groups (control group, treatment group, and model group), each with 24 rabbits. The model and treatment groups were first injected with an intravenous dose of horse serum, 10 ml/kg, three weeks later with an intravenous dose of 7.5 ml/kg, and two weeks later with an intramuscular dose of methylprednisolone, 45 mg/kg, three times in order to establish rabbit models of osteonecrosis. Concurrently, the treatment group was injected with intravenous doses of SF 20 mg/kg for two weeks, once per day. Three time points, Weeks 2, 4, and 8, were selected after modeling was completed. Osteonecrosis was verified by histopathology with haematoxylin-eosin (HE) staining. The apoptosis rate of osteonecrosis was observed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The apoptosis expressions of caspase-3 and Bcl-2 were analyzed by immunohistochemistry and Western blot. The rabbit models of osteonecrosis were successfully established and observed by HE staining. SF was effective in intervening in apoptosis and decreasing the apoptosis rate in femoral head necrosis by the immunohistochemistry and TUNEL assay (P<0.01). Western blot analysis indicated that there were statistical significances in the protein levels of caspase-3 and Bcl-2 (P<0.01). SF has a protective effect by reducing the incidence of early steroid-induced femoral head necrosis in rabbits, effectively intervening in apoptosis through decreasing caspase-3 expression and up-regulating Bcl-2 expression.

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References

  • Aaron, R.K., Gray, R.L., 2007. Osteonecrosis: Etiology, Natural History, Pathophysiology, and Diagnosis. In: Callaghan, J.J., Rosenberg, A.G., Rubash, J.E. (Eds.), The Adult Hip, 2nd Ed. Lippincott Williams & Wilkins, Philadelphia, p.463–476.

    Google Scholar 

  • Balasubashini, M.S., Rukkumani, R., Viswanathan, P., Menon, V.P., 2004. Ferulic acid alleviates lipid peroxidation in diabetic rats. Phytother. Res., 18(4):310–314. [doi:10.1002/ptr.1440]

    Article  PubMed  CAS  Google Scholar 

  • Bradway, J., Morrey, B., 1993. The natural history of the silent hip in bilateral atraumatic osteonecrosis. J. Arthropl., 8(4):383–387. [doi:10.1016/S0883-5403(06)80036-7]

    Article  CAS  Google Scholar 

  • Byun, C.H., Koh, J.M., Kim, D.K., Park, S.I., Lee, K.U., Kim, G.S., 2005. α-lipoic acid inhibits TNF-α-induced apoptosis in human bone marrow stromal cells. J. Bone Miner. Res., 20(7):1125–1135. [doi:10.1359/JBMR.050302]

    Article  PubMed  CAS  Google Scholar 

  • Cheng, C.Y., Su, S.Y., Tang, N.Y., 2008. Ferulic acid provides neuroprotection against oxidative stress-related apoptosis after cerebral ischemia/reperfusion injury by inhibiting ICAM-1 mRNA expression in rats. Brain Res., 1209: 136–150. [doi:10.1016/j.brainres.2008.02.090]

    Article  PubMed  CAS  Google Scholar 

  • Eberhardt, A.W., Yeager-Jones, A., Blair, H.C., 2001. Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid-treated rabbits. Endocrinology, 142(3):1333–1340. [doi:10.1210/en.142.3.1333]

    Article  PubMed  CAS  Google Scholar 

  • Felson, D.T., Anderson, J.J., 1987. Across-study evaluation of association between steroid dose and bolus steroids and avascular necrosis of bone. Lancet, 329(8538):902–906. [doi:10.1016/S0140-6736(87)92870-4]

    Article  Google Scholar 

  • Graf, E., 1992. Antioxidant potential of ferulic acid. Free Radic. Biol. Med., 13(4):435–448. [doi:10.1016/0891-5849(92)90184-I]

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto, I., Nakanishi, H., Shono, Y., Toda, M., Tsuda, H., Arase, S., 2002. Angiostatic effects of corticosteroid on wound healing of the rabbit ear. J. Med. Invest., 49(1–2):61–66.

    PubMed  Google Scholar 

  • Jones, L.C., Hungerford, D.S., 2004. Osteonecrosis: etiology, diagnosis, and treatment. Curr. Opin. Rheumatol., 16(4):443–449. [doi:10.1097/01.moo.0000127829.34643.fd]

    Article  PubMed  Google Scholar 

  • Karlnoski, R., Wilcock, D., Dickey, C., Ronan, V., Gordon, M.N., Zhang, W.R., Morgan, D., Taglialatela, G., 2007. Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection. Neurobiol. Dis., 25(1):179–188. [doi:10.1016/j.nbd.2006.09.007]

    Article  PubMed  CAS  Google Scholar 

  • Kerachian, M.A., Seguin, C., Harvey, E.J., 2009. Glucocorticoids in osteonecrosis of the femoral head: a new understanding of the mechanisms of action. J. Steroid Biochem. Mol. Biol., 114(3–5):121–128. [doi:10.1016/j.jsbmb.2009. 02.007]

    Article  PubMed  CAS  Google Scholar 

  • Khanduja, K.L., Avti, P.K., Kumar, S., Mittal, N., Sohi, K.K., Pathak, C.M., 2006. Anti-apoptotic activity of caffeic acid, ellagic acid and ferulic acid in normal human peripheral blood mononuclear cells: a Bcl-2 independent mechanism. Biochim. Biophys. Acta, 1760(2):283–289. [doi:10.1016/j.bbagen.2005.12.017]

    Article  PubMed  CAS  Google Scholar 

  • Kim, H.Y., Lee, S.M., 2012. Ferulic acid attenuates ischemia/reperfusion-induced hepatocyte apoptosis via inhibition of JNK activation. Eur. J. Pharm. Sci., 45(5):708–715. [doi:10.1016/j.ejps.2012.01.010]

    Article  PubMed  CAS  Google Scholar 

  • Koo, K.H., Kim, R., Kim, Y.S., Ahn, I.O., Cho, S.H., Song, H.R., Park, Y.S., Kim, H., Wang, G.J., 2002. Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin. Rheumatol., 21(4):299–303. [doi:10.1007/s100670200078]

    Article  PubMed  Google Scholar 

  • Kroemer, G., Martin, S.J., 2005. Caspase-independent cell death. Nat. Med., 11:725–730. [doi:10.1038/nm1263]

    Article  PubMed  Google Scholar 

  • Lavernia, C.J., Sierra, R.J., Grieco, F.R., 1999. Osteonecrosis of the femoral head. J. Am. Acad. Orthop. Surg., 7(4):250–261.

    PubMed  CAS  Google Scholar 

  • Matsui, M., Saito, S., Ohzono, K., Sugano, N., Saito, M., Takaoka, K., Ono, K., 1992. Experimental steroid-induced osteonecrosis in adult rabbits with hypersensitivity vasculitis. Clin. Orthop. Relat. Res., 277:61–72.

    PubMed  Google Scholar 

  • Maurya, D.K., Devasagayam, T.P., 2013. Ferulic acid inhibits gamma radiation-induced DNA strand breaks and enhances the survival of mice. Cancer Biother. Radiopharm., 28(1):51–57. [doi:10.1089/cbr.2012.1263]

    Article  PubMed  CAS  Google Scholar 

  • Maurya, D.K., Salvi, V.P., Nair, C.K., 2005. Radiation protection of DNA by ferulic acid under in vitro and in vivo conditions. Mol. Cell. Biochem., 280(1–2):209–217. [doi:10.1007/s11010-005-0170-4]

    Article  PubMed  CAS  Google Scholar 

  • Mazumder, S., Plesca, D., Almasan, A., 2008. Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. Methods Mol. Biol., 414:13–21. [doi:10.1007/978-1-59745-339-4_2]

    PubMed  CAS  Google Scholar 

  • Mendonça, D.M., Chimelli, L., Martinez, A.M., 2005. Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis. Braz. J. Med. Biol. Res., 38(6):925–933. [doi:10.1590/S0100-879X2005000600015]

    Article  PubMed  Google Scholar 

  • Mont, M.A., Hungerford, D.S., 1995. Non-traumatic avascular necrosis of the femoral head. J. Bone Joint Surg. (Am.), 77A(3):459–474.

    Google Scholar 

  • Mont, M.A., Jones, L.C., Hungerford, D.S., 2006. Nontraumatic osteonecrosis of the femoral head: ten years later. J. Bone Joint Surg. (Am.), 88(5):1117–1132. [doi:10.2106/JBJS.E.01041]

    Article  Google Scholar 

  • O’Brien, C.A., Jia, D., Plotkin, L.I., Bellido, T., Powers, C.C., Stewart, S.A., Manolagas, S.C., Weinstein, R.S., 2003. Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology, 145(4):1835–1841. [doi:10.1210/en.2003-0990]

    Article  PubMed  Google Scholar 

  • Park, S.K., Kang, H., Kwon, C.H., 2008. Caspase-dependent cell death mediates potent cytotoxicity of sulfide derivatives of 9-anilinoacridine. Anticancer Drugs, 19(4):381–389. [doi:10.1097/CAD.0b013e3282f9adb2]

    Article  PubMed  CAS  Google Scholar 

  • Perluigi, M., Joshi, G., Sultana, R., Calabrese, V., de Marco, C., Coccia, R., Cini, C., Butterfield, D.A., 2006. In vivo protective effects of ferulic acid ethyl ester against amyloid-β peptide 1–42-induced oxidative stress. J. Neurosci. Res., 84(2):418–426. [doi:10.1002/jnr.20879]

    Article  PubMed  CAS  Google Scholar 

  • Rojas, E., Carlini, R.G., Clesca, P., Arminio, A., Suniaga, O., de Elguezabal, K., Weisinger, J.R., Hruska, K.A., Bellorin-Font, E., 2003. The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling. Kidney Int., 63(5):1915–1923. [doi:10.1046/j.1523-1755.2003.00938.x]

    Article  PubMed  Google Scholar 

  • Rukkumani, R., Aruna, K., Varma, P.S., Menon, V.P., 2004. Influence of ferulic acid on circulatory prooxidant-antioxidant status during alcohol and PUFA induced toxicity. J. Physiol. Pharmacol., 55(3):551–561.

    PubMed  CAS  Google Scholar 

  • Sassa, S., Kikuchi, T., Shinoda, H., Suzuki, S., Kudo, H., Sakamoto, S., 2003. Preventive effect of ferulic acid on bone loss in ovariectomized rats. In Vivo, 17(3):277–280.

    PubMed  CAS  Google Scholar 

  • Srinivasan, M., Sudheer, A.R., Pillai, K.R., Kumar, P.R., Sudhakaran, P.R., Menon, V.P., 2006. Influence of ferulic acid on gamma-radiation induced DNA damage, lipid peroxidation and antioxidant status in primary culture of isolated rat hepatocytes. Toxicology, 228(2–3):249–258. [doi:10.1016/j.tox.2006.09.004]

    Article  PubMed  CAS  Google Scholar 

  • Sudheer, A.R., Muthukumaran, S., Kalpana, C., Srinivasan, M., Menon, V.P., 2007. Protective effect of ferulic acid on nicotine-induced DNA damage and cellular changes in cultured rat peripheral blood lymphocytes: a comparison with N-acetylcysteine. Toxicol. in Vitro, 21(4):576–585. [doi:10.1016/j.tiv.2006.11.006]

    Article  PubMed  CAS  Google Scholar 

  • Tsujimoto, Y., Shimizu, S., 2000. Bcl-2 family: life-or-death switch. FEBS lett., 466(1):6–10. [doi:10.1016/S0014-5793(99)01761-5]

    Article  PubMed  CAS  Google Scholar 

  • Wang, J., Yuan, Z., Zhao, H., 2011. Ferulic acid promotes endothelial cells proliferation through up-regulating cyclin D1 and VEGF. J. Ethnopharmacol., 137(2):992–997. [doi:10.1016/j.jep.2011.07.019]

    Article  PubMed  CAS  Google Scholar 

  • Wang, J.H., Yin, Q.S., Huang, Q.C., Wu, Y.S., 2004. Effect of vascular endothelial growth factor on angiogenesis and its regulation. Acad. J. Sec. Mil. Med. Univ., 25(2):210–212 (in Chinese).

    CAS  Google Scholar 

  • Weinstein, R.S., Nicholas, R.W., Manolagas, S.C., 2000. Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip. J. Clin. Endocrinol. Metab., 85(8):2907–2912. [doi:10.1210/jc.85.8.2907]

    Article  PubMed  CAS  Google Scholar 

  • Wenk, G.L., McGann, G.K., Hauss, W.B., Ronchetti, D., Maucci, R., Rosi, S., Gasparini, L., Ongini, E., 2004. Attenuation of chronic neuroinflammation by a nitric oxide-releasing derivative of the antioxidant ferulic acid. J. Neurochem., 89(2):484–493. [doi:10.1111/j.1471-4159.2004.02359.x]

    Article  PubMed  CAS  Google Scholar 

  • Yogeeta, S.K., Gnanapragasam, A., Senthilkumar, S., Subhashini, R., Devaki, T., 2006. Synergistic salubrious effect of ferulic acid and ascorbic acid on membrane-bound phosphatases and lysosomal hydrolases during experimental myocardial infarction in rats. Life Sci., 80(3):258–263. [doi:10.1016/j.lfs.2006.09.012]

    Article  PubMed  CAS  Google Scholar 

  • Zaidi, M., Sun, L., Robinson, L.J., Tourkova, I.L., Liu, L., Wang, Y., Zhu, L., Liu, X., Li, J., Peng, Y., et al., 2010. ACTH protects against glucocorticoid-induced osteonecrosis of bone. PNAS, 107(19):8782–8787. [doi:10.1073/pnas.0912176107]

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, the Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong University, Xi’an, 710004, China

    Lei Tian, Xiao-qian Dang, Chun-sheng Wang, Pei Yang, Chen Zhang & Kun-zheng Wang

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  1. Lei Tian
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  2. Xiao-qian Dang
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  3. Chun-sheng Wang
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Correspondence to Kun-zheng Wang.

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Tian, L., Dang, Xq., Wang, Cs. et al. Effects of sodium ferulate on preventing steroid-induced femoral head osteonecrosis in rabbits. J. Zhejiang Univ. Sci. B 14, 426–437 (2013). https://doi.org/10.1631/jzus.B1200311

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  • DOI: https://doi.org/10.1631/jzus.B1200311

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