The Effect of Resveratrol on Bone Status in Rats with Bile Duct Obstruction


Objective: We studied the influence of bile duct obstruction (BDO) after 28 days on bone metabolism status and their modification by resveratrol in male Wistar rats. Methods: The rats were divided into 3 groups: Sham group with laparotomy and vehiculum application, group BDO—bile duct obstruction and vehiculum application, and group RBDO—bile duct obstruction and resveratrol application (10 mg/kg dose of resveratrol orally once daily). The bone mineral density (BMD; g/cm2) and body composition were measured by dual energy X-ray absorptiometry. The physiccal strenght of femur was examined by controlled break biomechanical testing. The osteocalcin, procollagen type I N-terminal propeptide (PINP) and carboxy-terminal collagen crosslinks (CTX) were analysed by EIA in the bone tissue homogenate. Results: The total BMD was lower in group BDO (0.176 ± 0.005; p = 0.01) and R-BDO (0.181 ± 0.004; p = 0.052) vs Sham (0.209 ± 0.003). BMD of femur diaphysis in BDO group decreased significantly (p = 0.01) but not in R-BDO animals (p = 0.052). Body fat (g, median) was lower in BDO (19.0) and R-BDO (26.0) than in Sham (35.0). The force needed for fracture of femurs (N) significantly decreased in BDO (154 ± 6) and R-BDO (151 ± 13) vs Sham group (208 ± 7). The force needed for neck fracture decreased in BDO (105 ± 3) and R-BDO (115 ± 8) vs Sham (135 ± 9). The osteocalcin decrease in group R-BDO (2.9 ± 0.1) vs Sham (3.7 ± 0.4). Higher PINP/CTX were in BDO (20 ± 5/0.49 ± 0.08) and R-BDO (30 ± 4/0.55 ± 0.07) vs Sham (16 ± 4/0.48 ± 0.11). Conclusions: Our findings suggest that subchronic bile duct obstruction decreased body fat quantity and BMD with decrease of bone rigidity. Resveratrol showed protective effect on liver injury and consequently positive influence on bone tissue.

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H. Zivna, S. Micuda, E. Brcakova-Dolezelova and P. Zivny, "The Effect of Resveratrol on Bone Status in Rats with Bile Duct Obstruction," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 1, 2013, pp. 46-51. doi: 10.4236/ojemd.2013.31007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] G. Wariaghli, F. Allali, A. El Maghraoui and N. Hajjaj-Hassouni, “Osteoporosis in Patients with Primary Biliary Cirrhosis,” European Journal of Gastroenterology & Hepatology, Vol. 22, No. 12, 2010, pp. 1397-1401.
[2] V. Goel and P. Kar, “Hepatic Osteodystrophy,” Trop Gastroenterol, Vol. 31, No. 2, 2010, pp. 82-86.
[3] N. Gua?abens, D. Cerdá, A. Monegal, F. Pons, L. Caballera, P. Peris and A. Parés, “Low Bone Mass and Severity of Cholestasis Affect Fracture Risk in Patients with Primary Biliary Cirrhosis,” Gastroenterology, Vol. 138, No. 7, 2010, pp. 2348-2356. doi:10.1053/j.gastro.2010.02.016
[4] G. López-Larramona, A. J. Lucendo, S. González-Castillo and J. M. Tenias, “Hepatic Osteodystrophy: An Important Matter for Consideration in Chronic Liver Disease,” World Journal of Hepatology, Vol. 3, No. 12, 2011, pp. 300-307. doi:10.4254/wjh.v3.i12.300
[5] F. A. Pereira, I. Facincani, V. Jorgetti, L. N. Ramalho, J. B. Volpon, L. M. Dos Reis and F. J. de Paula, “Etiopathogenesis of Hepatic Osteodystrophy in Wistar Rats with Cholestatic Liver Disease,” Calcified Tissue International, Vol. 85, No. 1, 2009, pp. 75-83. doi:10.1007/s00223-009-9249-3
[6] M. Weinreb, R. D. Pollak and Z. Ackerman, “Experimental Cholestatic Liver Disease through Bile-Duct Ligation in Rats Results in Skeletal Fragility and Impaired Osteoblastogenesis,” Journal of Hepatology, Vol. 40, No. 3, 2004, pp. 385-390. doi:10.1016/j.jhep.2003.11.032
[7] Z. Ackerman, M. Weinreb, G. Amir and R. D. Pollak, “Bone Mineral Metabolism and Histomorphometry in Rats with Cholestatic Liver Disease,” Liver, Vol. 22, No. 2, 2002, pp. 166-172. doi:10.1046/j.0106-9543.2002.01566.x
[8] D. J. Leeming, D. V. Larsen, C. Zhang, Y. Hi, S. S. Veidal, R. H. Nielsen, K. Henriksen, Q. Zheng, V. Barkholt, B. J. Riis, I. Byrjalsen, P. Qvist and M. A. Karsdal, “Enzyme-Linked Immunosorbent Serum Assays (ELISAs) for Rat and Human N-Terminal Pro-Peptide of Collagen Type I (PINP)—Assessment of Corresponding Epitopes,” Clinical Biochemistry, Vol. 43, No. 15, 2010, pp. 1249-1256. doi:10.1016/j.clinbiochem.2010.07.025
[9] F. Melchior and H. Kindl, “Grapevine Stilbene Synthase cDNA Only Slightly Differing from Chalcone Synthese cDNA Is Expressed in Escherichia Coli into a Catalytically Active Enzyme,” FEBS Letters, Vol. 268, No. 1, 1990, pp. 17-20. doi:10.1016/0014-5793(90)80961-H
[10] W. Yu, Y. C. Fu and W. Wang, “Cellular and Molecular Effects of Resveratrol in Health and Disease,” Journal of Cellular Biochemistry, Vol. 113, No. 3, 2012, pp. 752-759. doi:10.1002/jcb.23431
[11] S. Gómez-Zorita, A. Fernández-Quintela, M. T. Macarulla, L. Aguirre, E. Hájina, L. Bujana, F. Milagro, J. A. Martínez and M. P. Portillo, “Resveratrol Attenuates Steatosis in Obese Zucker Rats by Decreasing Fatty Acid Availability and Reducing Oxidative Stress,” British Journal of Nutrition, Vol. 107, No. 2, 2012, pp. 202-210. doi:10.1017/S0007114511002753
[12] T. K. Lin, L. T. Huang, Y. H. Huang, M. M. Tiao, K. S. Tang and C. W. Liou, “The Effect of the Red Wine Polyphenol Resveratrol on a Rat Model of Biliary Obstructed Cholestasis: Involvement of Anti-Apoptotic Signalling, Mitochondrialbiogenesis and the Induction of Autophagy,” Apoptosis, Vol. 17, No. 8, 2012, pp. 871-879. doi:10.1007/s10495-012-0732-3
[13] C. C. Chan, L. Y. Cheng, C. L. Lin, Y. H. Huang, H. C. Lin and F. Y. Lee, “The Protective Role of Natural Phytoalexin Resveratrol on Inflammation, Fibrosis and Regeneration in Cholestatic Liver Injury,” Molecular Nutrition & Food Research, Vol. 55, No. 12, 2011, pp. 1841-1849. doi:10.1002/mnfr.201100374
[14] K. Kupisiewicz, P. Boissy, B. M. Abdallah, F. D. Hansen, R. G. Erben, J. F. Savouret, K. S?e, T. L. Andersen, T. Plesner and J. M. Delaisse, “Potential of Resveratrol Analogues as Antagonists of Osteoclasts and Promoters of Osteoblasts,” Calcified Tissue International, Vol. 87, No. 5, 2010, pp. 437-449. doi:10.1007/s00223-010-9399-3
[15] M. Shakibaei, C. Buhrmann and A. Mobasheri, “Resveratrol-Mediated SIRT-1 Interactions with p300 Modulate Receptor Activator of NF-Kappab Ligand (RANKL) Activation of NF-kappaB Signaling and Inhibit Osteoclastogenesis in Bone-Derived Cells,” The Journal of Biological Chemistry, Vol. 26, No. 9, 2011, pp. 1173-1185.
[16] R. L. Duncan, K. A. Akanbi and M. C. Farach-Carson, “Calcium Signals and Calcium Channels in Osteoblastic Cells,” Seminars in Nephrology, Vol. 18, No. 2, 1998, pp. 178-190.
[17] J. M. Fernández-Real and W. Ricart, “Osteocalcin: A new Link between Bone and Energy Metabolism. Some Evolutionary Clues,” Current Opinion in Clinical Nutrition & Metabolic Care, Vol. 14, No. 4, 2011, pp. 360-366. doi:10.1097/MCO.0b013e328346df4e
[18] F. Szalay, P. Lakatos, J. Németh, M. Abonyi, B. Büki, G. Tarján and I. Holló, “Decreased Serum Osteocalcin Level in Non-Alcoholic and Alcoholic Chronic Liver Diseases,” Orvosi Hetilap, Vol. 132, No. 24, 1991, pp. 1301-1305.
[19] M. Herrmann, N. Umanskaya, B. Wildemann, G. Colaianni, T. Widmann, A. Zallone and W. Hermann, “Stimulation of Osteoblast Activity by Homocysteine,”Journal of Cellular and Molecular Medicine, Vol. 12, No. 4, 2008, pp. 1205-1210. doi:10.1111/j.1582-4934.2008.00104.x
[20] E. Brcakova, L. Fuksa, J. Cermanova, G. Kolouchova, M. Hroch, P. Hirsova, J. Martinkova, F. Staud and S. Micuda, “Alteration of Methotrexate Biliary and Renal Elimination during Extrahepatic and Intrahepatic Cholestasis in Rats,” Biological and Pharmaceutical Bulletin, Vol. 32, No. 12, 2009, pp. 1978-1985. doi:10.1248/bpb.32.1978
[21] C. H. Turner and D. B. Burr, “Basic Biomechanical Measurements of Bone: A Tutorial,” Bone, Vol. 14, No. 4, 1993, pp. 595-608. doi:10.1016/8756-3282(93)90081-K
[22] G. Alberdi, V. M. Rodríguez, J. Miranda, M. T. Macarulla, N. Arias, C. Andrés-Lacueva and M. P. Portillo, “Changes in White Adipose Tissue Metabolism Induced by Resveratrol in Rats,” Nutrition & Metabolism, Vol. 8, No. 1, 2011, p. 29. doi:10.1186/1743-7075-8-29
[23] T. Miyahara, L. Schrum, R. Rippe, S. Xiong, H. F. Yee Jr., K. Motomura, F. A. Anania, T. M. Willson and H. Tsukamoto, “Peroxisome Proliferator-Activated Receptors and Hepatic Stellate Cell Activation,” The Journal of Biological Chemistry, Vol. 275, No. 46, 2000, pp. 35715-35722. doi:10.1074/jbc.M006577200
[24] J. J. Potter, L. Womack, E. Mezey and F. A. Anania, “Transdifferentiation of Rat Hepatic Stellate Cells Results in Leptin Expression,” Biochemical and Biophysical Research Communications, Vol. 244, No. 2, 1998, pp. 178-182. doi:10.1006/bbrc.1997.8193
[25] K. Mizutani, K. Ikeda, Y. Kawai and Y. Yamori, “Resveratrol Attenuates Ovariectomy-Induced Hypertension and Bone Loss in Stroke-Prone Spontaneously Hypertensive Rats,” Journal of Nutritional Science and Vitaminology, Vol. 46, No. 2, 2000, pp. 78-83. doi:10.3177/jnsv.46.78
[26] S. Sehmisch, F. Hammer, J. Christoffel, D. Seidlova-Wuttke, M. Tezval, W. Wuttke, K. M. Stuermer and E. K. Stuermer, “Comparison of the Phytohormones Genistein, Resveratrol and 8-Prenylnaringenin as Agents for Preventing Osteoporosis,” Planta Medica, Vol. 74, No. 8, 2008, pp. 794-801. doi:10.1055/s-2008-1074550
[27] S. U. Singh, R. F. Casper, P. C. Fritz, B. Sukhu, B. Ganss, B. Girard Jr., J. F. Savouret and H. C. Tenenbaum, “Inhibition of Dioxin Effects on Bone Formation in Vitro by a Newly Described Aryl Hydrocarbon Receptor Antagonist, Resveratrol,” Journal of Endocrinology, Vol. 167, No. 1, 2000, pp. 183-195. doi:10.1677/joe.0.1670183
[28] X. He, G. Andersson, U. Lindgren and Y. Li, “Resveratrol Prevents RANKL-Induced Osteoclast Differentiation of Murine Osteoclast Progenitor RAW 264.7 Cells through Inhibition of ROS Production,” Biochemical and Biophysical Research Communications, Vol. 401, No. 3, 2010, pp. 356-362. doi:10.1016/j.bbrc.2010.09.053
[29] C. Bruedigam, M. Eijken, M. Koedam, H. Chiba and J. P. van Leeuwen, “Opposing Actions of Rosiglitazone and Resveratrol on Mineralization in Human Vascular Smooth Muscle Cells,” Journal of Molecular and Cellular Cardiology, Vol. 51, No. 5, 2011, pp. 862-871. doi:10.1016/j.yjmcc.2011.07.020
[30] J. L. Su, C. Y. Yang, M. Zhao, M. L. Kuo and M. L. Yen, “Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-Tumor Activity of Resveratrol,” The Journal of Biological Chemistry, Vol. 282, No. 27, 2007, pp. 19385-19398. doi:10.1074/jbc.M702452200
[31] Z. P. Liu, W. X. Li, B. Yu, J. Huang, J. Sun, J. S. Huo and C. X. Liu, “Effects of Trans-Resveratrol from polygonum Cuspidatum on Bone Loss Using the Ovariectomized Rat Model,” Journal of Medicinal Food, Vol. 8, No. 1, 2005, pp. 14-19. doi:10.1089/jmf.2005.8.14
[32] L. L. Chen, S. X. Wang, Y. Dai, P. Buckoreelall, P. Zhang, H. H. Zhang and W. Kong, “Effect of Catch-Up Growth by Various Dietary Patterns and Resveratrol Intervention on Bone Status,” Experimental Biology and Medicine, Vol. 237, No. 3, 2012, pp. 297-304. doi:10.1258/ebm.2011.011296

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