Magnesium Lithospermate B Reduces Inflammatory Response in a Mouse Model of Hepatic Ischemia–Reperfusion Injury
Tóm tắt
It has been well proved that acute inflammatory response and hepatocellular apoptosis contributed to the pathogenesis of liver ischemia reperfusion (IR) injury. A vast amount of research has demonstrated that magnesium lithospermate B (MLB) has potent anti-apoptosis and potential anti-inflammatory pharmacological properties. However, it has not previously been examined whether MLB can attenuate hepatic IR injury. Firstly, the optimal dose of MLB to protect against hepatic IR injury was determined using hepatic IR model in mice. Then, the effect of MLB on IR-induced inflammatory response was detected in detail. We found that MLB exhibited protective effect from the beginning of 50 mg/kg and culminated at the doses of 100 and 200 mg/kg. The alanine aminotransferase and aspartate aminotransferase levels in MLB group were markedly decreased. Severe hepatocellular swelling/necrosis, sinusoidal/vascular congestion and inflammatory cell infiltration were seen and a large number of apoptotic cells were found in the liver samples from Saline group, while minimal damage and very few apoptotic cells were noted in the samples from MLB group. Kuppfer cells infiltration, myeloperoxidase activity and mRNA level of CD11b in MLB group was significantly decreased. Serum TNF-a and IL-6, and mRNA expression of CXCL-10 and ICAM-1 was markedly decreased in the samples from MLB group. Inflammatory signaling pathway activation was largely prevented in MLB group. MLB can significantly attenuate IR-induced hepatocellular damage and hepatocellular apoptosis by preventing inflammatory signaling pathways activation, inflammatory mediators expression and macrophage and neutrophil infiltration.
Tài liệu tham khảo
Shen, X. D., Gao, F., Ke, B., Zhai, Y., Lassman, C. R., Tsuchihashi, S., et al. (2005). Inflammatory responses in a new mouse model of prolonged hepatic cold ischemia followed by arterialized orthotopic liver transplantation. Liver Transplantation, 11, 1273.
Jaeschke, H. (2006). Mechanisms of liver injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia–reperfusion and other acute inflammatory conditions. American Journal of Physiology Gastrointestinal and Liver Physiology, 290, G1083.
Yamanouchi, K., Eguchi, S., Kamohara, Y., Yanaga, K., Okudaira, S., Tajima, Y., et al. (2007). Glycine reduces hepatic warm ischaemia-reperfusion injury by suppressing inflammatory reactions in rats. Liver International, 27, 1249.
Li, J. Y., Gu, X., Zhang, W. H., Jia, S., & Zhou, Y. (2009). GdCl3 abates hepatic ischemia–reperfusion injury by inhibiting apoptosis in rats. Hepatobiliary Pancreatic Diseases International, 8, 518.
Rajesh, M., Pan, H., Mukhopadhyay, P., Batkai, S., Osei-Hyiaman, D., Hasko, G., et al. (2007). Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. Journal of Leukocyte Biology, 82, 1382.
Bignotto, L., Rocha, J., Sepodes, B., Eduardo-Figueira, M., Pinto, R., Chaud, M., et al. (2009). Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia-reperfusion in the rat. British Journal of Nutrition, 102, 126.
Cheng, T. O. (2007). Cardiovascular effects of Danshen. International Journal of Cardiology, 121, 9.
Zhou, L., Zuo, Z., & Chow, M. S. (2005). Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. Journal of Clinical Pharmacology, 45, 1345.
Fu, J., Huang, H., Liu, J., Pi, R., Chen, J., & Liu, P. (2007). Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis. European Journal of Pharmacology, 568, 213.
Hur, K. Y., Seo, H. J., Kang, E. S., Kim, S. H., Song, S., Kim, E. H., et al. (2008). Therapeutic effect of magnesium lithospermate B on neointimal formation after balloon-induced vascular injury. European Journal of Pharmacology, 586, 226.
Kim, D. H., Jeon, S. J., Jung, J. W., Lee, S., Yoon, B. H., Shin, B. Y., et al. (2007). Tanshinone congeners improve memory impairments induced by scopolamine on passive avoidance tasks in mice. European Journal of Pharmacology, 574, 140.
Liu, X., Chen, R., Shang, Y., Jiao, B., & Huang, C. (2009). Superoxide radicals scavenging and xanthine oxidase inhibitory activity of magnesium lithospermate B from Salvia miltiorrhiza. Journal of Enzyme Inhibition and Medicinal Chemistry, 24, 663.
Kim, S. H., Kim, S. H., Choi, M., Lee, Y., Kim, Y. O., Ahn, D. S., et al. (2010). Natural therapeutic magnesium lithospermate B potently protects the endothelium from hyperglycaemia-induced dysfunction. Cardiovascular Research, 87, 713.
Yang, L. M., Xiao, Y. L., & Ou-Yang, J. H. (2003). Inhibition of magnesium lithospermate B on the c-Jun N-terminal kinase 3 mRNA expression in cardiomyocytes encountered ischemia/reperfusion injury. Yao Xue Xue Bao, 38, 487.
Kim, J. B., Han, A. R., Park, E. Y., Kim, J. Y., Cho, W., Lee, J., et al. (2007). Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-kappaB inactivation in RAW 264.7 macrophage cells. Biological and Pharmaceutical Bulletin, 30, 2345.
Han, J. Y., Fan, J. Y., Horie, Y., Miura, S., Cui, D. H., Ishii, H., et al. (2008). Ameliorating effects of compounds derived from Salvia miltiorrhiza root extract on microcirculatory disturbance and target organ injury by ischemia and reperfusion. Pharmacology and Therapeutics, 117, 280.
Hashimoto, K., Minagawa, H., & Yanagi, Y. (2003). Caspase-dependent apoptosis in fulminant hepatic failure induced by herpes simplex virus in mice. Journal of Hepatology, 39, 773.
Yan, B. Z., Wang, W., Chen, L. Y., Bi, M. R., Lu, Y. J., Li, B. X., et al. (2009). Role of cathepsin B-mediated apoptosis in fulminant hepatic failure in mice. World Journal of Gastroenterology, 15, 1231.
Amaral, F. A., Fagundes, C. T., Guabiraba, R., Vieira, A. T., Souza, A. L., Russo, R. C., et al. (2007). The role of macrophage migration inhibitory factor in the cascade of events leading to reperfusion-induced inflammatory injury and lethality. American Journal of Pathology, 171, 1887.
Friedewald, J. J., & Rabb, H. (2004). Inflammatory cells in ischemic acute renal failure. Kidney International, 66, 486.
Shiratori, Y., Kiriyama, H., Fukushi, Y., Nagura, T., Takada, H., Hai, K., et al. (1994). Modulation of ischemia–reperfusion-induced hepatic injury by Kupffer cells. Digestive Diseases and Sciences, 39, 1265.
Walsh, K. B., Toledo, A. H., Rivera-Chavez, F. A., Lopez-Neblina, F., & Toledo-Pereyra, L. H. (2009). Inflammatory mediators of liver ischemia–reperfusion injury. Experimental and Clinical Transplantation, 7, 78.
Jung, M., Lee, H. C., Ahn, C. W., Park, W., Choi, S., Kim, H., et al. (2002). Effective isolation of magnesium lithospermate B and its inhibition of aldose reductase and fibronectin on mesangial cell line. Chemical Pharmaceutical Bulletin (Tokyo), 50, 1135.
Lam, F. F., Yeung, J. H., Kwan, Y. W., Chan, K. M., & Or, P. M. (2006). Salvianolic acid B, an aqueous component of danshen (Salvia miltiorrhiza), relaxes rat coronary artery by inhibition of calcium channels. European Journal of Pharmacology, 553, 240.
Suzuki, S., Toledo-Pereyra, L. H., Rodriguez, F. J., & Cejalvo, D. (1993). Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury: modulating effects of FK506 and cyclosporine. Transplantation, 55, 1265.
Shen, X. D., Ke, B., Zhai, Y., Tsuchihashi, S. I., Gao, F., Duarte, S., et al. (2007). Diannexin, a novel annexin V homodimer, protects rat liver transplants against cold ischemia–reperfusion injury. American Journal of Transplantation, 7, 2463.
Song, S., Shen, X., Tang, Y., Wang, Z., Guo, W., Ding, G., et al. (2010). Sinomenine pretreatment attenuates cold ischemia/reperfusion injury in rats: the role of heme oxygenase-1. International Immunopharmacology, 10, 679.
Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−∆∆CT method. Methods, 25, 402.