Abstract
Hepatic ischemia reperfusion (HIR) not only results in liver injury, but also leads to endotoxemia, which aggravates HIR-induced liver injury and dysfunction, or even causes liver failure. Taurine has been shown to protect organs from ischemia reperfusion or endotoxin by its anti-oxidant and anti-inflammatory activities. The aim of this study was to investigate whether taurine could attenuate endotoxin-induced acute liver injury after HIR. Wistar rats subjected to 30 min of hepatic ischemia followed by reperfusion and lipopolysaccharide (LPS) (0.5 mg/kg) administration, exhibited liver dysfunction (elevated serum levels of ALT, AST and LDH) and hepatic histopathological alteration. The serum levels of TNF-α and production of myeloperoxidase (MPO) and malondialdehyde (MDA) in liver tissues and apoptosis of hepatocytes were also increased after the combination of HIR and LPS. However, pre-administration of taurine protected livers from injury induced by the combination of HIR + LPS as the histological score, apoptotic index, MPO activity and production of MDA in liver tissues, and serum levels of AST, ALT, LDH and TNF-α, were significantly reduced. The expression of caspase-3, Fas and Fas ligand was upregulated in homogenates of livers from rats subjected to HIR and LPS, and this elevated expression could be inhibited by taurine. In summary, the results further emphasize the potential utilization of taurine in protecting livers against endotoxin-induced injury especially after HIR, by its anti-inflammatory, anti-oxidative and anti-apoptotic activities.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arii S, Shibagaki M, Takahashi S, Taki Y, Yokoo N, Jikko A, Tanaka J, Kamiyama Y, Takasan H, Ozawa K (1985) Changes in the reticuloendothelial phagocytic function after partial hepatectomy. J Lab Clin Med 105:668–672
Bellezzo JM, Britton RS, Bacon BR, Fox ES (1996) LPS-mediated NF-kappa beta activation in rat Kupffer cells can be induced independently of CD14. Am J Physiol 270:G956–G961
Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310. doi:10.1016/S0076-6879(78)52032-6
Colletti LM, Green M (2001) Lung and liver injury following hepatic ischemia/reperfusion in the rat is increased by exogenous lipopolysaccharide which also increases hepatic TNF production in vivo and in vitro. Shock 16:312–319
Dauphinee SM, Karsan A (2006) Lipopolysaccharide signaling in endothelial cells. Lab Invest 86:9–22. doi:10.1038/labinvest.3700366
Deutschman CS, Haber BA, Andrejko K, Cressman DE, Harrison R, Elenko E, Taub R (1996) Increased expression of cytokine-induced neutrophil chemoattractant in septic rat liver. Am J Physiol 271:R593–R600
Erdamar H, Tuikozkan N, Ekremoglu M, Kurt Y, Yaman H (2007) The effects of taurine on polymorphonuclear leukocyte functions in endotoxemia. Amino Acids 33:581–585. doi:10.1007/s00726-007-0543-y
Erdem A, Sevgili AM, Akbiyik F, Atilla P, Cakar N, Balkanci ZD, Iskit AB, Guc MO (2008) The effect of taurine on mesenteric blood flow and organ injury in sepsis. Amino Acids 35:403–410. doi:10.1007/s00726-007-0622-0
Fernandez ED, Flohe S, Siemers F, Nau M, Ackermann M, Ruwe M, Schade FU (2000) Endotoxin tolerance protects against local hepatic ischemia/reperfusion injury in the rat. J End Res 6:321–328
Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G (1995) Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Am J Clin Nutr 61:1115–1119
Green DR (2000) Apoptotic pathways: paper wraps stone blunts scissors. Cell 102:1–4. doi:10.1016/S0092-8674(00)00003-9
Hu YH, Lin CL, Huang YW, Liu PE, Hwang DF (2007) Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients. Amino Acids 35:469–473. doi:10.1007/s00726-007-0565-5
Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163
Jaeschke H (2000) Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol 15:718–724. doi:10.1046/j.1440-1746.2000.02207.x
Jiang H, Meng F, Li J, Sun X (2005) Anti-apoptosis effects of oxymatrine protect livers from warm ischemia reperfusion injury in rats. World J Surg 29:1397–1401. doi:10.1007/s00268-005-7885-y
Jiang H, Meng F, Li W, Tong L, Qiao H, Sun X (2007) Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery 141:32–40. doi:10.1016/j.surg.2006.03.024
Kaibori M, Yanagida H, Uchida Y, Yokoigawa N, Kwon AH, Okumura T, Kamiyama Y (2004) Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats. Transplant Proc 36:1973–1974. doi:10.1016/j.transproceed.2004.08.061
Kingston R, Kelly CJ, Murray P (2004) The therapeutic role of taurine in ischemia-reperfusion injury. Curr Pharm Des 10:2401–2410. doi:10.2174/1381612043384015
Kono H, Fujii H, Matsuda M, Yamamoto M, Matsumoto Y (2001) Gadolinium chloride prevents mortality in hepatectomized rats given endotoxin. J Surg Res 96:204–210. doi:10.1006/jsre.2001.6099
Krammer PH (2000) CD95’s deadly mission in the immune system. Nature 407:789–795. doi:10.1038/35037728
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489. doi:10.1016/S0092-8674(00)80434-1
Licht C, Kriegesmann E, Minor T, Wingenfeld P, Isselhard W, Michalk DV (1998) Influence of taurine supplementation on ischemic preservation of the isolated rat kidney. Adv Exp Med Biol 442:201–206
McLaughlin R, Bowler D, Kelly CJ, Kay E, Bouchier-Hayes D (2000) Taurine protects against early and late skeletal muscle dysfunction secondary to ischaemia reperfusion injury. Eur J Surg 166:375–379. doi:10.1080/110241500750008916
O’Flaherty L, Bouchier-Hayes DJ (1999) Immunonutrition and surgical practice. Proc Nutr Soc 58:831–837. doi:10.1017/S0029665199001123
Rakotoambinina B, Marks L, Badran AM, Igliki F, Thuillier F, Crenn P, Messing B, Darmaun D (2004) Taurine kinetics assessed using (1, 2–13 C2) taurine in healthy adult humans. Am J Physiol Endocrinol Metab 287:E255–E262. doi:10.1152/ajpendo.00333.2003
Raschke P, Massoudy P, Becker BF (1995) Taurine protects the heart from neutrophil-induced reperfusion injury. Free Radic Biol Med 19:461–471. doi:10.1016/0891-5849(95)00044-X
Redmond HP, Stapleton PP, Neary P, Bouchier-Hayes D (1998) Immunonutrition: the role of taurine. Nutrition 14:599–604. doi:10.1016/S0899-9007(98)00097-5
Sakaguchi T, Nakamura S, Suzuki S, Oda T, Ichiyama A, Baba S, Okamoto T (1999) Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats. Hepatology 30:959–967. doi:10.1002/hep.510300414
Schaffer S, Azuma J, Takahashi K, Mozaffari M (2003) Why is taurine cytoprotective? Adv Exp Med Biol 526:307–321
Seki S, Habu Y, Kawamura T, Takeda K, Dobashi H, Ohkawa T, Hiraide H (2000) The liver as a crucial organ in the first line of host defense: the roles of Kupffer cells, natural killer (NK) cells and NK1.1 Ag+ T cells in T helper immune responses. Immunol Rev 174:35–46. doi:10.1034/j.1600-0528.2002.017404.x
Selzner M, Rudiger HA, Sindram D, Madden J, Clavien PA (2000) Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology 32:1280–1288. doi:10.1053/jhep.2000.20528
Su GL (2002) Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. Am J Physiol 283:G256–G265
Suzuki S, Nakamura S, Serizawa A, Sakaguchi T, Konno H, Muro H, Kosugi I, Baba S (1996) Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy. Hepatology 24:219–225. doi:10.1002/hep.510240135
Tang B, Qiao H, Meng F, Sun X (2007) Glycyrrhizin attenuates endotoxin-induced acute liver injury after partial hepatectomy in rats. Braz J Med Biol Res 40:1637–1646. doi:10.1590/S0100-879X2006005000173
Tong L, Li J, Qiao H, Jiang H, Meng F, Sun X (2005) Taurine protects against ischemia reperfusion injury in rabbit livers. Transplant Proc 38:1575–1579. doi:10.1016/j.transproceed.2006.02.057
Tsoulfas G, Takahashi Y, Ganster RW, Yagnik G, Guo Z, Fung JJ, Murase N, Geller DA (2002) Activation of the lipopolysaccharide signaling pathway in hepatic transplantation preservation injury. Transplantation 74:7–13. doi:10.1097/00007890-200207150-00003
Tsuji K, Kwon AH, Yoshida H, Qiu Z, Kaibori M, Okumura T, Kamiyama Y (2005) Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats. J Hepatol 42:94–101. doi:10.1016/j.jhep.2004.09.018
Watanabe M, Chijiiwa K, Kameoka N, Yamaguchi K, Kuroki S, Tanaka M (2000) Gadolinium pre-treatment decreases survival and impair liver regeneration after partial hepatectomy under ischemiaReperfusion in rats. Surgery 127:456–463. doi:10.1067/msy.2000.104744
Waterfield CJ, Turton JA, Scales MD, Timbrell JA (1993) Reduction of liver taurine by beta-alaine treatment increases carbon tetrachloride toxicity. Toxicology 77:7–20. doi:10.1016/0300-483X(93)90133-D
Wettstein M, Haussinger D (2000) Taurine attenuates cold ischemia-reoxygenation injury in rat liver. Transplantation 69:2290–2296. doi:10.1097/00007890-200006150-00012
Wettstein M, Häussinger D (1997) Cytoprotection by the osmolytes betaine and taurine in ischemia-reoxygenation injury in the perfused rat liver. Hepatology 26:1560–1566
Wu G, Yang J, Sun C, Luan X, Shi J, Hu J (2008) Effect of taurine on alcoholic liver disease in rats. Amino Acids. doi:10.1007/s00726-008-0101-2
Xing HC, Li LJ, Xu KJ, Shen T, Chen YB, Chen Y, Fu SZ, Sheng JF, Chen CL, Wang JG, Yan D, Dai FW, Sha XY (2005) Effects of Salvia miltiorrhiza on intestinal microflora in rats with ischemia reperfusion liver injury. Hepatobiliary Pancreat Dis Int 4:274–280
Zhang J, Niu X (1994) Changes of monoamines, purines and amino acids in rat striatum as measured by intercerebral microdialysis during ischemia/reperfusion. Chin Med Sci J 9:225–229
Zhang F, Tong L, Qiao H, Dong X, Qiao G, Jiang H, Sun X (2008) Taurine attenuates multiple organ injury induced by intestinal ischemia reperfusion in rats. J Surg Res 149:101–109. doi:10.1016/j.jss.2007.12.781
Acknowledgments
The work was supported by the National Natural Scientific Foundation of China (30571808, 30571753, 30872987), a Collaborative Fund for Oversea Scholars from The Science and Technology Bureau of Heilongjiang Province, China (WH05C02), and the Creative Foundation of Daqing High-tech Industrial Development Zone, China (DQCX06YF001).
Author information
Authors and Affiliations
Corresponding authors
Additional information
F. Zhang and Y. Mao contributed equally to this work.
Rights and permissions
About this article
Cite this article
Zhang, F., Mao, Y., Qiao, H. et al. Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. Amino Acids 38, 237–245 (2010). https://doi.org/10.1007/s00726-009-0233-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-009-0233-z