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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.

[1]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.

[2]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.

[3]Bradway, J., Morrey, B., 1993. The natural history of the silent hip in bilateral atraumatic osteonecrosis. J. Arthropl., 8(4):383-387.

[4]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.

[5]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.

[6]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.

[7]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.

[8]Graf, E., 1992. Antioxidant potential of ferulic acid. Free Radic. Biol. Med., 13(4):435-448.

[9]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.

[10]Jones, L.C., Hungerford, D.S., 2004. Osteonecrosis: etiology, diagnosis, and treatment. Curr. Opin. Rheumatol., 16(4):443-449.

[11]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.

[12]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.

[13]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.

[14]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.

[15]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.

[16]Kroemer, G., Martin, S.J., 2005. Caspase-independent cell death. Nat. Med., 11:725-730.

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

[18]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.

[19]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.

[20]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.

[21]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.

[22]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.

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

[24]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.

[25]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.

[26]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.

[27]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.

[28]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.

[29]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.

[30]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.

[31]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.

[32]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.

[33]Tsujimoto, Y., Shimizu, S., 2000. Bcl-2 family: life-or-death switch. FEBS lett., 466(1):6-10.

[34]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.

[35]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).

[36]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.

[37]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.

[38]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.

[39]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.