Protective Effect of Baicalin against Hepatic Ischemia/Reperfusion Injury in Alcoholic Fatty Liver

알코올성 지방간에서 Baicalin의 허혈 및 재관류로 인한 간 손상 보호 효과

  • Received : 2012.07.24
  • Accepted : 2012.08.10
  • Published : 2012.08.31

Abstract

This study examined the effects of baicalin, a bioactive flavonoid isolated from Scutellaria baicalensis, on hepatic injury caused by ischemia/reperfusion (I/R) in alcoholic fatty liver. Rats were fed an ethanol liquid diet or a control isocaloric diet for 5 weeks, and then subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Baicalin (200 mg/kg) was administered intraperitoneally 24 and 1 h before ischemia. After reperfusion, baicalin attenuated the increase in serum alanine aminotransferase activity. The levels of cytosolic cytochrome c protein expression, caspase-3 activity, the number of apoptotic cells increased after reperfusion, which were higher in ethanol-fed animals, were attenuated by baicalin. Following I/R, the hepatic lipid peroxidation was elevated, whereas hepatic glutathione content was decreased. These changes attenuated by baicalin. In ethanol-fed animals, baicalin augmented the increases in heme oxygenase-1 protein and mRNA expressions, and nuclear Nrf2 expression. In conclusion, our findings suggest that baicalin ameliorates I/R-induced hepatocellular damage by suppressing apoptosis and oxidative stress in alcoholic fatty liver.

Keywords

References

  1. Yun, N., Kang, J. W. and Lee, S. M. : Protective effects of chlorogenic acid against ischemia/reperfusion injury in rat liver: Molecular evidence of its antioxidant and antiinflammatory properties. J. Nutr. Biochem. in press.
  2. Kim, H. Y. and Lee, S. M. : Ferulic acid attenuates ischemia/ reperfusion-induced hepatocyte apoptosis via inhibition of JNK activation. Eur. J. Pharm. Sci. 45, 708 (2012).
  3. Ijaz, S., Winslet, M. C. and Seifalian, A. M. : The effect of consecutively larger doses of L-arginine on hepatic microcirculation and tissue oxygenation in hepatic steatosis. Microvasc. Res. 78, 206 (2009).
  4. D'Alessandro, A. M., Kalayoglu, M., Sollinger, H. W., Hoffmann, R. M., Reed, A., Knechtle, S. J., Pirsch, J. D., Hafez, G. R., Lorentzen, D. and Belzer, F. O. : The predictive value of donor liver biopsies for the development of primary nonfunction after orthotopic liver transplantation. Transplantation 51, 157 (1991).
  5. Selzner, M. and Clavien, P. A. : Fatty liver in liver transplantation and surgery. Semin. Liver Dis. 21, 105 (2001).
  6. Koneru, B., Reddy, M. C., de la Torre, A. N., Patel, D., Ippolito, T. and Ferrante, R. J. : Studies of hepatic warm ischemia in the obese zucker rat. Transplantation 59, 942 (1995)
  7. Nakano, H., Nagasaki, H., Barama, A., Boudjema, K., Jaeck, D., Kumada, K., Tatsuno, M., Baek, Y., Kitamura, N., Suzuki, T. and Yamaguchi, M. : The effects of N-acetylcysteine and antiintercellular adhesion molecule-1 monoclonal antibody against ischemia-reperfusion injury of the rat steatotic liver produced by a choline-methionine-deficient diet. Hepatology 26, 670 (1997).
  8. Yamada, S., Iida, T., Tabata, T., Nomoto, M., Kishikawa, H., Kohno, K. and Eto, S. : Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic necrosis after ischemia-reperfusion in rat. Hepatology 32, 278 (2000).
  9. Taira, Z., Yabe, K., Hamaguchi, Y., Hirayama, K., Kishimoto, M., Ishida, S. and Ueda, Y. : Effects of sho-saiko-to extract and its components, baicalin, baicalein, glycyrrhizin and glycyrrhetic acid, on pharmacokinetic behavior of salicylamide in carbon tetrachloride intoxicated rats. Food Chem. Toxicol. 42, 803 (2004).
  10. Gao, W., Bentley, R. C., Madden, J. F. and Clavien, P. A. : Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation. Hepatology 27, 1652 (1998).
  11. Wang, G. F., Wu, Z. F., Wan, L., Wang, Q. T. and Chen, F. M. : Influence of baicalin on the expression of receptor activator of nuclear factor-kappaB ligand in cultured human periodontal ligament cells. Pharmacology 77, 71 (2006).
  12. Chang, C. P., Huang, W. T., Cheng, B. C., Hsu, C. C. and Lin, M. T. : The flavonoid baicalin protects against cerebrovascular dysfunction and brain inflammation in experimental heatstroke. Neuropharmacology 52, 1024 (2007).
  13. Park, S. W., Lee, C. H., Kim, Y. S., Kang, S. S., Jeon, S. J., Son, K. H. and Lee, S. M. : Protective effect of baicalin against carbon tetrachloride-induced acute hepatic injury in mice. J. Pharmacol. Sci. 106, 136 (2008).
  14. Zhang, Z. J., Li, P., Wang, Z., Li, P. T., Zhang, W. S., Sun, Z. H., Zhang, X. J. and Wang, Y. Y. : A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury. Brain Res. 1123, 188 (2006).
  15. Peng, X. D., Dai, L. L., Huang, C. Q., He, C. M. and Chen, L. J. : Correlation between anti-fibrotic effect of baicalin and serum cytokines in rat hepatic fibrosis. World J. Gastroenterol. 15, 4720 (2009).
  16. Kim, S. J. and Lee, S. M. : Effect of baicalin on toll-like receptor 4-mediated ischemia/reperfusion inflammatory responses in alcoholic fatty liver condition. Toxicol. Appl. Pharmacol. 258, 43 (2012).
  17. Lieber, C. S. and DeCarli, L. M. : Liquid diet technique of ethanol administration: 1989 update. Alcohol Alcohol. 24, 197 (1989).
  18. Folch, J., Lees, M. and Sloane Stanley, G. H. : A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497 (1957).
  19. Buege, J. A. and Aust, S. D. : Microsomal lipid peroxidation. Methods Enzymol. 52, 302 (1978).
  20. Morin, D., Pires, F., Plin, C. and Tillement, J. P. : Role of the permeability transition pore in cytochrome C release from mitochondria during ischemia-reperfusion in rat liver. Biochem. Pharmacol. 68, 2065 (2004).
  21. Urena, M. A., Ruiz-Delgado, F. C., Gonzalez, E. M., Segurola, C. L., Romero, C. J., Garcia, I. G., Gonzalez-Pinto, I. and Gomez Sanz, R. : Assessing risk of the use of livers with macro and microsteatosis in a liver transplant program. Transplant. Proc. 30, 3288 (1998).
  22. de la M Hall, P., Lieber, C. S., DeCarli, L. M., French, S. W., Lindros K. O., Jarvelainen H., Bode C., Parlesak A. and Bode J. C. : Models of alcoholic liver disease in rodents: A critical evaluation. Alcohol. Clin. Exp. Res. 25, 254S (2001).
  23. Sasaki, H., Matsuno, T., Tanaka, N. and Orita, K. : Activation of apoptosis during the reperfusion phase after rat liver ischemia. Transplant. Proc. 28, 1908 (1996).
  24. Bernardi, P., Petronilli, V., Di Lisa, F. and Forte, M. : A mitochondrial perspective on cell death. Trends Biochem. Sci. 26, 112 (2001).
  25. Derdak, Z., Lang, C. H., Villegas, K. A., Tong, M., Mark, N. M., de la Monte, S. M. and Wands, J. R. : Activation of p53 enhances apoptosis and insulin resistance in a rat model of alcoholic liver disease. J. Hepatol. 54, 164 (2011).
  26. Han, J. Y., Fan, J. Y., Horie, Y., Miura, S., Cui, D. H., Ishii, H., Hibi, T., Tsuneki, H. and Kimura, I. : Ameliorating effects of compounds derived from salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacol. Ther. 117, 280 (2008).
  27. Lopez-Neblina, F., Toledo, A. H. and Toledo-Pereyra, L. H. : Molecular biology of apoptosis in ischemia and reperfusion. J. Invest. Surg. 18, 335 (2005).
  28. Prokopenko, V. M., Partsalis, G. K., Pavlova, N. G., Burmistrov, S. O. and Arutyunyan, A. V. : Glutathione-dependent system of antioxidant defense in the placenta in preterm delivery. Bull. Exp. Biol. Med. 133, 442 (2002).
  29. Duckers, H. J., Boehm, M., True, A. L., Yet, S. F., San, H., Park, J. L., Clinton Webb, R., Lee, M. E., Nabel, G. J. and Nabel, E. G. : Heme oxygenase-1 protects against vascular constriction and proliferation. Nat. Med. 7, 693 (2001).
  30. Lin, Q., Weis, S., Yang, G., Weng, Y. H., Helston, R., Rish, K., Smith, A., Bordner, J., Polte, T., Gaunitz, F. and Dennery, P. A. : Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress. J. Biol. Chem. 282, 20621 (2007).
  31. Scapagnini, G., Foresti, R., Calabrese, V., Giuffrida Stella, A. M., Green, C. J. and Motterlini, R. : Caffeic acid phenethyl ester and curcumin: A novel class of heme oxygenase-1 inducers. Mol. Pharmacol. 61, 554 (2002).
  32. Yun, N., Eum, H. A. and Lee, S. M. : Protective role of heme oxygenase-1 against liver damage caused by hepatic ischemia and reperfusion in rats. Antioxid. Redox Signal. 13, 1503 (2010).
  33. Itoh, K., Mochizuki, M., Ishii, Y., Ishii, T., Shibata, T., Kawamoto, Y., Kelly, V., Sekizawa, K., Uchida, K. and Yamamoto, M. : Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-delta(12,14)-prostaglandin j(2). Mol. Cell. Biol. 24, 36 (2004).
  34. Leonard, M. O., Kieran, N. E., Howell, K., Burne, M. J., Varadarajan, R., Dhakshinamoorthy, S., Porter, A. G., O'Farrelly, C., Rabb, H. and Taylor, C. T. : Reoxygenationspecific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemiareperfusion injury. FASEB J. 20, 2624 (2006).