Potential Therapeutic Role of Osteopontin Inhibition in Liver Fibrosis -Induced by Thioacetamide in Rats | ||||
| Journal of Applied Veterinary Sciences | ||||
| Article 1, Volume 2, Issue 1, October 2017, Page 1-8 PDF (648.17 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/javs.2017.62129 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Ramadan A. 1; Nehal A. Afifi1; Nemat Z. Yassin2; Rehab F. Abdel-Rahman2; Sahar S. Abd El-Rahman3; Hany M. Fayed* 2
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| 1Pharmacology Department, Faculty of Veterinary Medicine, Cairo University, Egypt. | ||||
| 2Pharmacology Department, Medical Division, National Research Centre, Giza, Egypt. | ||||
| 3Pathology Department, Faculty of Veterinary Medicine, Cairo University, Egypt. | ||||
| Abstract | ||||
| To examine the effect of osteopontin inhibition by tranilast on liver fibrosis, four groups of rats were used throughout this study. Group I (Control group): rats received the solvent. Liver fibrosis was induced in Groups II, III, and IV by thioacetamide (TAA; 200mg/kg, ip) twice weekly for 6 weeks. Group II served as (TAA group). Groups III and IV (Treatment groups): rats were given tranilast for 6 weeks after TAA discontinuation. Liver osteopontin (OPN), transforming growth factor-β (TGF-β1), tumor necrosis factor alpha (TNF-α), alpha-smooth muscle actin (ɑ-SMA)), reduced glutathione (GSH), superoxide dismutase (SOD) and lipid peroxidation (MDA) were measured. Additionally, expression of α-smooth muscle actin (SMA) and caspase (Cas)-3 were assigned immunohistochemically. Treatment with tranilast prevented the development of hepatic fibrosis and the activation of stellate cells, and down-regulated the expression of genes for osteopontin and osteopontin-target molecules, including TGF-β and TNF-α and α-SMA.Tranilast significantly decreased MDA and increased levels of GSH, and SOD. Our findings suggest that targeting osteopontin with tranilast represents a new mode of therapy for liver fibrosis. | ||||
| Keywords | ||||
| Osteopontin; Liver fibrosis; apoptosis; antioxidant | ||||
| References | ||||
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ABDELAZIZ, R.R., ELKASHEF, W.F., SAID, E. 2015. Tranilast reduces serum IL-6 and IL-13 and protects against thioacetamide-induced acute liver injury and hepatic encephalopathy. Environmental toxicology and pharmacology 40: 259-267. ALEX, M., SAUGANTH, PAUL, M.V., ABHILASH, M., MATHEWS, V.V., ANILKUMAR, T.V., NAIR, R.H. 2014. Astaxanthin modulates osteopontin and transforming growth factor beta1 expression levels in a rat model of nephrolithiasis: a comparison with citrate administration. BJU international 114: 458-466. ARFFA, M.L. 2016. Epigallocatechin-3-Gallate Upregulates miR-221 to Inhibit Osteopontin-Dependent Hepatic Fibrosis. PloS one 11: e0167435. BANSAL, R., Nagórniewicz, B., RNIEWICZ, B., PRAKASH, J. 2016. Clinical Advancements in the Targeted Therapies against Liver Fibrosis. Mediators of inflammation 2016: 16. BULAJ, G., KORTEMME, T., GOLDENBERG, D.P. 1998. Ionization-reactivity relationships for cysteine thiols in polypeptides. Biochemistry 37: 8965-8972. CHEN, H.W., HUANG, Y.J., YAO, H.T., LII, C.K. 2012. Induction of Nrf2-dependent Antioxidation and Protection Against Carbon Tetrachloride-induced Liver Damage by Andrographis Herba (chuan xin lian) Ethanolic Extract. Journal of traditional and complementary medicine 2: 211-219. DE FUSCO, C. 2017. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis. Stem Cells Int 2017: 4045238. ELLMAN, G.L. 1959. Tissue sulfhydryl groups. Archives of biochemistry and biophysics 82: 70-77. FAUSTHER, M., PRITCHARD, M.T., POPOV, Y.V., BRIDLE, K. 2017. Contribution of Liver Nonparenchymal Cells to Hepatic Fibrosis: Interactions with the Local Microenvironment. BioMed research international 2017: 4. FTAHY, M.M., LATIF, A., ALALKAMY, E.F., EL-BATRAWI, F.A., GALAL, A.H., KHATAB, H.M. 2013. Antifibrotic potential of a selective COX-2 inhibitor (celecoxib) on liver fibrosis in rats. Comparative Clinical Pathology 22: 425-430. HSU, S.M., RAINE, L., FANGER, H. 1981. The use of antiavidin antibody and avidin-biotin-peroxidase complex in immunoperoxidase technics. American journal of clinical pathology 75: 816-821. HUANG, H., ZHANG, X.F., ZHOU, H.J., XUE, Y.H., DONG, Q.Z., YE, Q.H., QIN, L.X. 2010. Expression and prognostic significance of osteopontin and caspase-3 in hepatocellular carcinoma patients after curative resection. Cancer science 101: 1314-1319. HUANG, L.F., WEN, C., XIE, G., CHEN, CY. 2014. Effect of tranilast on myocardial fibrosis in mice with viral myocarditis]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 16: 1154-1161. HUNG, Y.P., LEE, C.L. 2017. Higher Anti-Liver Fibrosis Effect of Cordyceps militaris-Fermented Product Cultured with Deep Ocean Water via Inhibiting Proinflammatory Factors and Fibrosis-Related Factors Expressions. Marine drugs 15. JING, J., ZHAO, J.Y., HUA, B., XUE, M.Q., ZHU, Y.F., LIU, G., WANG, Y.H., PENG, X.D. 2015. Inhibitory effect of flavonoids from Glycyrrhiza uralensis on expressions of TGF-beta1 and Caspase-3 in thioacetamide-induced hepatic fibrosis in rats]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 40: 3034-3040. KON, S., NAKAYAMA, Y., MATSUMOTO, N., ITO, K., KANAYAMA, M., KIMURA, C., KOURO, H., ASHITOMI, D., MATSUDA, T., UEDE, T. 2014. A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for alpha9beta1 integrin is involved in the anti-type II collagen antibody-induced arthritis. PloS one 9: e116210. KOTHARI, A.N., ARFFA, M.L., CHANG, V., BLACKWELL, R.H., SYN, W.K., ZHANG, J., MI, Z., KUO, P.C. 2016. Osteopontin-A Master Regulator of Epithelial-Mesenchymal Transition. Journal of clinical medicine 5. KOYAMA, Y., XU, J., LIU, X., BRENNER, D.A. 2016. New Developments on the Treatment of Liver Fibrosis. Digestive diseases 34: 589-596. LEE, Y.A., WALLACE, M.C., FRIEDMAN, S.L. 2015. Pathobiology of liver fibrosis: a translational success story. Gut 64: 830-841. LENGA, Y., KOH, A., PERERA, A.S., MCCULLOCH, C.A., SODEK, J., ZOHAR, R. 2008. Osteopontin expression is required for myofibroblast differentiation. Circulation research 102: 319-327. NAGATE, T., TAMURA, T., SATO, F., KURODA, J., NAKAYAMA, J., SHIBATA, N. 2007. Tranilast suppresses the disease development of the adjuvant- and streptococcal cell wall-induced arthritis in rats. Journal of pharmacological sciences 105: 48-56. PRITCHETT, J. 2012. Osteopontin is a novel downstream target of SOX9 with diagnostic implications for progression of liver fibrosis in humans. Hepatology 56: 1108-1116. RUIZ-LARREA, M.B., LEAL, A.M., LIZA, M., LACORT, M., DE GROOT, H. 1994. Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59: 383-388. SAID, E., ELKASHEF, W.F., ABDELAZIZ, R.R. 2016. Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity. Canadian journal of physiology and pharmacology 94: 347-358. SWIDERSKI, K., TODOROV, M., GEHRIG, S.M., NAIM, T., CHEE, A., STAPLETON, D.I., KOOPMAN, R., LYNCH, G.S. 2014. Tranilast administration reduces fibrosis and improves fatigue resistance in muscles of mdx dystrophic mice. Fibrogenesis & tissue repair 7: 1. TAO, Y., HU, L., LI, S., LIU, Q., WU, X., LI, D., FU, P., WEI, D., LUO, Z. 2011. Tranilast prevents the progression of chronic cyclosporine nephrotoxicity through regulation of transforming growth factor beta/Smad pathways. Transplantation proceedings 43: 1985-1988. ZHOU, W.C., ZHANG, Q.B., QIAO, L. 2014. Pathogenesis of liver cirrhosis. World journal of gastroenterology 20: 7312-7324. | ||||
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