Purpose: Gut permeability and microvascular injur y following ischaemia/reperfusion (IR) have been implicated in the systemic inflammatory response syndrome (SIRS) and multiple organ failure (MOF). Taurine (TAU), a sulfur-containing amino acid, is a powerful antioxidant and regulator of intracellular calcium and several studies have established that treatment with TAU protects cerebral, cardiac and testicular tissue from (IR) injury . This study investigates the protective effect of taurine in an experimental model of I/R-induced gut injury in rats . Methods: Sprague-Dawley rats were randomized into three groups: Control, I/R, TAU + I/R. TAU was given by gavage or intravenous injection before I/R. Ischaemia was induced by cross-clamping superior mesenteric and coeliac vascular pedicle for 20 - 30 min, followed by 60 - 180 min reperfusion. Gut permeability, blood flux, tissue oedema, leucocytes infiltration and eNOS expression were measured at 3 hrs following reperfusion using FD4. Leukocyte-endothelial interactions were determined by intra-vital microscopy during I/R. <i> In vitro </i> studies assessed the protective effect of TAU on endothelial cell function and survival. Results: Treatment with TAU significantly attenuated IR-induced gut hyper permeability, tissue oedema, leukocyte adhesion and infiltration. TAU also prevented the reduction in gut blood flow, leuko cyte rolling velocity and eNOS expression induced by IR. TAU protects against I/R -induced endothelial cell injury by reduced anti-oxidant activity and modulation of eNOS expression and intracellular calcium fluxes. Conclusions: TAU protects the gut from intestinal barrier dysfunction induced by surgical I/R.
Yellon, D.M. and Hausenloy, D.J. (2007) Myocardial Reperfusion Injury. The New England Journal of Medicine, 357, 1121-1135. https://doi.org/10.1056/NEJMra071667
Saikumar, P., Dong, Z., Weinberg, J.M. and Venkatachalam, M.A. (1998) Mechanisms of Cell Death in Hypoxia/Reoxygenation Injury. Oncogene, 17, 3341-3349. https://doi.org/10.1038/sj.onc.1202579
Kalogeris, T., Baines, C.P., Krenz, M. and Korthuis, R.J. (2012) Cell Biology of Ischemia/Reperfusion Injury. International Review of Cell and Molecular Biology, 298, 229-317.
Varadarajan, R, Golden-Mason, L., Young, L., et al. (2004) Nitric Oxide in Early Ischaemia Reperfusion Injury during Human Orthotopic Liver Transplantation. Transplantation, 78, 250-256. https://doi.org/10.1097/01.tp.0000128188.45553.8c
Parks, D.A. and Granger, D.N. (1986) Contributions of Ischemia and Reperfusion to Mucosal Lesion Formation. American Journal of Physiology, 250, G749-G753.
Javadpor, M., Kelly, C.J., Chen, G., Stokes, K., Leahy, A. and Boucher-Hayes, D.J. (1998) Thermotolerance Induces Heat Shock Protein 72 Expression and Protects against Ischaemia-Reperfusion-Induced Lung Injury. British Journal of Surgery, 85, 943-946. https://doi.org/10.1046/j.1365-2168.1998.00722.x
Neary, P. and Redmond, H.P. (1999) Ischaemia-Reperfusion Injury and the Systemic Inflammatory Response Syndrome. In: Grace, P.A. and Mathie, R.T. Eds., Ischaemia-Reperfusion Injury, Blackwell Science, Oxford, 123-136.
Tamion, F., Richard, V., Lyoumi, S., Daveau, M., Bonmarchand, G., Leroy, J., Thuillez, C. and Lebreton, J.P. (1997) Gut Ischemia and Mesenteric Synthesis of Inflammatory Cytokines after Hemorrhagic or Endotoxic Shock. American Journal of Physiology, 273, G314-G321.
Liu, Z., Qin, H., Yang, Z., Xia, Y., Liu, W., Yang, J., Jiang, Y., Zhang, H., Yang, Z., Wang, Y. and Zheng, Q. (2011) Randomised Clinical Trial: The Effects of Perioperative Probiotic Treatment on Barrier Function and Post-Operative Infectious Complications in Colorectal Cancer Surgery—A Double-Blind Study. Alimentary Pharmacology & Therapeutics, 33, 50-63.
Gatt, M., Reddy, B.S. and Macfie, J. (2007) Bacterial Translocation in the Critically Ill—Evidence and Methods of Prevention. Alimentary Pharmacology & Therapeutics, 25, 741-757. https://doi.org/10.1111/j.1365-2036.2006.03174.x
Rodrigues, S.F. and Granger, D. (2010) Role of Blood Cells in Ischaemia-Reperfusion Induced Endothelial Barrier Failure. Cardiovascular Research, 87, 291-299. https://doi.org/10.1093/cvr/cvq090
Arnould, T., Michiels, C., Alexandre, I. and Remacle, J. (1992) Effects of Hypoxia upon Intracellular Calcium Concentration of Human Endothelial Cells. Journal of Cellular Physiology, 152, 215-221. https://doi.org/10.1002/jcp.1041520127
Kohli, V., Madden, J.F., Bentley, R.C. and Clavien, P. (1999) Calpain Mediates Ischemic Injury of the Liver through Modulation of Apoptosis and Necrosis. Gastroenterology, 116, 168-178. https://doi.org/10.1016/S0016-5085(99)70241-6
Ali, M.H., Schlidt, S.A., Chandel, N.S., Hynes, K.L., Schumacker, P.T. and Gewertz, B.L. (1999) Endothelial Permeability and IL-6 Production during Hypoxia: Role of ROS in Signal Transduction. American Journal of Physiology, 277, L1057-1065.
Yang, W. and Block, E.R. (1995) Effect of Hypoxia and Reoxygenation on the Formation and Release of Reactive Oxygen Species by Porcine Pulmonary Artery Endothelial Cells. Journal of Cellular Physiology, 164, 414-423. https://doi.org/10.1002/jcp.1041640222
Zulueta, J.J., Sawhney, R., Yu, F.S., Cote, C.C. and Hassoun, P.M. (1997) Intracellular Generation of Reactive Oxygen Species in Endothelial Cells Exposed to Anoxia-Reoxygenation. American Journal of Physiology, 272, L897-902.
Granger, D.N. and Korthuis, R.J. (1995) Physiologic Mechanisms of Postischemic Tissue Injury. Annual Review of Physiology, 57, 311-332. https://doi.org/10.1146/annurev.ph.57.030195.001523
Grishman, M.B., Hernandez, L.A. and Granger, D.N. (1989) Adenosine Inhibits Ischemia-Reperfusion-Induced Leukocyte Adherence and Extravasation. American Journal of Physiology, 257, H334-H339.
Raschke, P., Massoudy, P. and Bercker, B.F. (1995) Taurine Protects the Heart from Neutriphi-Induced Reperfusion Injury. Free Radical Biology & Medicine, 19, 461-471.
Wettstein, M. and Haussinger, D. (2000) Taurine Attenuate Cold Ischemia-Reoxygenation Injury in Rat Liver. Transplantation, 69, 2290-2296. https://doi.org/10.1097/00007890-200006150-00012
Egan, B.M., Chen, G., Kelly, C.J. and Bouchier-Hayes, D.J. (2001) Taurine Attenuates LPS-Induced Rolling and Adhesion in Rat Microcirculation. Journal of Surgical Research, 95, 85-91. https://doi.org/10.1006/jsre.2000.6005
Redmond, H.P., Wang, J.H. and Bouchier-Hayes, D. (1996) Taurine Attenuates Nitric Oxide and Reactive Oxygen Intermediate-Dependent Hepatocyte Injury. Archives of Surgery, 131, 1280-1288. https://doi.org/10.1001/archsurg.1996.01430240034004
Wang, J.H., Redmond, H.P., Watson, R.W.G., Condron, C. and Bouchier-Hayes, D. (1996) The Beneficial Effect of Taurine on the Prevention of Human Endothelial Cell Death. Shock, 6, 331-338. https://doi.org/10.1097/00024382-199611000-00006
Wu, Q.D., Wang, J.H., Fennessy, F., Redmond, H.P. and Bouchier-Hayes, D. (1999) Taurine Prevents High-Glucose-Induced Human Vascular Endothelial Cell Apoptosis. American Journal of Physiology, 277, C1229-C1238.
Fennessy, F.M., Moneley, D.S., Wang, J.H., Kelly, C.J. and Bouchier-Hayes, D. (2003) Taurine and Vitamin C Modify Monocyte and Endothelial Dysfunction in Young Smokers. Circulation, 107, 410-415. https://doi.org/10.1161/01.CIR.0000046447.72402.47
Nakashima, T., Seto, Y., Nakajima, T., Shima, T., Sakamoto, Y., Cho, N., Sano, A., Iwai, M., Kagawa, K., Okanoue, T. and Kashima, K. (1990) Calcium-Associated Cytoprotective Effect of Taurine on the Calcium and Oxygen Paradoxes in Isolated Rat Hepatocytes. Liver International, 10, 167-172. https://doi.org/10.1111/j.1600-0676.1990.tb00453.x
Oriyanhan, W., Yamazaki, K., Miwa, S., Takaba, K., Ikeda, T. and Komeda, M. (2005) Taurine Prevents Myocardial Ischemia/Reperfusion-Induced Oxidative Stress and Apoptosis in Prolonged Hypothermic Rat Heart Preservation. Heart and Vessels, 20, 278-285. https://doi.org/10.1007/s00380-005-0841-9
Gosling, M., Harley, S.L., Turner, R.J., Carey, N. and Powell, J.T. (1998) Human Saphenous Vein Endothelial Cells Express a Tetrodotoxin-Resistant, Voltaged Soldium Current. The Journal of Biological Chemistry, 273, 21084-21090. https://doi.org/10.1074/jbc.273.33.21084
Cuzzocrea, S., Zingarelli, B., Costantino, G., Szabo, A., Salzman, A.L., Caputi, A. and Szabo, C. (1997). Beneficial Effects of 3-Aminobenzamine, an Inhibitor of Poly (ADP-Ribose) Synthease in a Rat Model of Splanchic Artery Occlusion and Reperfusion. British Journal of Pharmacology, 121, 1065-1074. https://doi.org/10.1038/sj.bjp.0701234
Sims, C.A., Wattanasirichaigoon, S., Menconi, M.J., Ajami, A.M. and Fink, M.P. (2001) Ringer’s Ethyl Pyruvate Solution Ameliorates Ischemia/Reperfusion-Induced Intestinal Mucosal Injury in Rats. Critical Care Medicine, 29, 1513-1518.
Ivey, C.L., Williams, F.M., Collins, P.D., Jose, P.J. and Williams, T.J. (1995) Neutrophil Chemoattractants Generated in Two Phases during Reperfusion of Ischemic Myocardium in the Rabbit. Evidence for a Role for C5a and Interleukin-8. Journal of Clinical Investigation, 95, 2720-2728. https://doi.org/10.1172/JCI117974
Stempien-Oterro, A., Karsan, A., Carol, J., Xiang, H., Eunson, T., Morrison, R.S., Kay, M., Winn, R. and Harlan, J. (1999) Mechanism of Hypoxia-Induced Endothelial Cell Death Role of p53 in Apoptosis. The Journal of Biological Chemistry, 274, 8039-8045. https://doi.org/10.1074/jbc.274.12.8039
McQuillan, L.P., Leung, G.K., Marsden, P.A., Kostyk, S.K. and Kourembanas, S. (1994) Hypoxia Inhibits Expression of eNOS via Transcriptional and Posttranscriptional Mechanisms. American Journal of Physiology, 267, H1921-H1927.
Li, D., Yang, B. and Mehta, J.L. (1999) Tumor Necrosis Factor-α Enhances Hypoxia-Reoxygenation-Mediated Apoptosis in Cultured Human Coronary Artery Endothelial Cells: Critical Role of Protern Kinase C. Cardiovascular Research, 42, 805-813. https://doi.org/10.1016/S0008-6363(98)00342-3
Wiles, M.E., Hechtman, H.B., Morel, N.M.L. and Shepro, D. (1993) Hypoxia Reoxygenation-Induced Injury of Cultured Pulmonary Microvessel Endothelial Cells. Journal of Leukocyte Biology, 53, 490-497.
Amarente-Menes, G.P., Finucance, D.M., Cotter, T.G., Salvesen, G.S. and Green, D.R. (1998) Anti-Apoptotic Oncogenes Prevent Caspase-Dependent and Independent Commitment for Cell Death. Cell Death and Differentiation, 5, 298-306. https://doi.org/10.1038/sj.cdd.4400354
Leist, M., Single, B., Castoldi, A.F., Kuhnlem, S. and Nicotera, P. (1997) Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision between Apoptosis and Necrosis. The Journal of Experimental Medicine, 185, 1481-1486. https://doi.org/10.1084/jem.185.8.1481
Green, D.R. and Reed, J.C. (1998) Mitochondria and Apoptosis. Science, 281, 1309-1312. https://doi.org/10.1126/science.281.5381.1309
McCord, J.M. (1985) Oxygen-Derived Free Radicals in Postischemic Tissue Injury. The New England Journal of Medicine, 312, 159-163. https://doi.org/10.1056/NEJM198501173120305
Paradies, G., Petrosillo, G., Pistolese, M., Di Venosa, N., Federici, A. and Ruggiero, F.M. (2004) Decrease in Mitochondrial Complex I Activity in Ischemic/Reperfused Rat Heart: Involvement of Reactive Oxygen Species and Cardiolipin. Circulation Research, 94, 53-59. https://doi.org/10.1161/01.res.0000109416.56608.64
Hardy, D.L., Clark, J.B., Darley-Usmar, V.M. and Smith, D.R. (1990) Reoxygenation of the Hypoxic Myocardium Causes a Mitochondrial Complex I Defect. Biochemical Society Transactions, 18, 549. https://doi.org/10.1042/bst0180549
Nulton-Persson, A.C. and Szweda, L.I. (2001) Modulation of Mitochondrial Function by Hydrogen Peroxide. The Journal of Biological Chemistry, 276, 23357-23361. https://doi.org/10.1074/jbc.M100320200
Kim, Y.M., Kim, T.H., Seol, D.W., Talanian, R.V. and Billiar, T.R. (1998) Nitric Oxide Supression of Apoptosis Occurs in Association with an Inhibition of Bcl-2 Cleavage and Cytochrome C Release. The Journal of Biological Chemistry, 273, 31437-31441. https://doi.org/10.1074/jbc.273.47.31437
Michalk, D.V., Wingenfeld, P., Licht, C., Ugur, T. and Siar, L.F. (1996) The Mechanisms of Taurine Mediated Protection against Cell Damage Induced by Hypoxia and Reoxygenation. In: Huxtable, R.J., J. Azuma, Kuriyama, K., Nakagawa, M. and Baba, A., Eds., Taurine 2: Basic and Clinical Aspects. Advances in Experimental Medicine and Biology, Vol. 403, Springer US, 223-232. https://doi.org/10.1007/978-1-4899-0182-8_24
Suschek, C.V., Krischel, V., Bruch-Gerharz, D., Berendji, D., Krutmann, J., Kroncke, K.D. and Kolb-Bachofen, V. (1999) Nitric Oxide Fully Protects against UVA-Induced Apoptosis in Tight Correlation with Bcl-2 Up-Regulation. The Journal of Biological Chemistry, 274, 6130-6137. https://doi.org/10.1074/jbc.274.10.6130
Kim, Y.M., Bombeck, C.A. and Billiar, T.R. (1999) Nitric Oxide as Bifunctional Regulator of Apoptosis. Circulation Research, 84, 253-256. https://doi.org/10.1161/01.RES.84.3.253
Dimmeler, S., Haendeler, J., Nehls, M. and Zeiher, AM. (1997) Supression of Apotosis by Nitric Oxide via Inhibition of Interleukin-1-Beta-Conventing Enzyme (ICE)-Like and Cysyeine Protease Protein(CCP)-32-Like Protases. The Journal of Experimental Medicine, 185, 601. https://doi.org/10.1084/jem.185.4.601
Kim, Y.M., Talanian, R.V. and Billiar, T.R. (1997) Nitric Oxide Inhibits Apoptosis by Preventing Increases in Caspas-3-Like Activity via Two Distinct Mechanisms. The Journal of Biological Chemistry, 272, 31138-31148. https://doi.org/10.1074/jbc.272.49.31138
Rossig, L., Haendeler, J., Hermann, C., Malchow, P., Urbich, C., Zeiher, A.M. and Dimmeler, S. (2000) Nitric Oxide Down-Regulates MKP-3 mRNA Level Involvement in Endothelial Cell Protection from Apoptosis. The Journal of Biological Chemistry, 275, 25502-25507. https://doi.org/10.1074/jbc.M002283200
Sukhotnik, I., Aranovich, I., Ben Shahar, Y., Bitterman, N., Pollak, Y., Berkowitz, D., Chepurov, D., Coran, A.G. and Bitterman, A. (2016) Effect of Taurine on Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat. Pediatric Surgery International, 32, 161-168. https://doi.org/10.1007/s00383-015-3828-3
Lindbom, L., Xie, X. and Raud, J. (1992) Chemoattractant-Induced Leucocyte Adhesion to Vascular Endothelium in Vivo Is Critically Dependent on Initial Leucocyte Rolling. Acta Physiologica, 146, 415-421. https://doi.org/10.1111/j.1748-1716.1992.tb09442.x
Zibari, G.B., Brown, M.F., Burney, D.L., Granger, D.N. and McDonald, J.C. (1998) Role of P-Selectin in the Recruitment of Leucocytes in Mouse Liver Exposed to Ischemia and Reperfusion. Transplantation Proceedings, 30, 2327-2330. https://doi.org/10.1016/S0041-1345(98)00641-1
Moore, E.E., Moore, F.A., Franciose, R.J., Kim, F.J., Biffl, W.L. and Banerjee, A. (1994) The Postischemic Gut Serves as a Priming Bed for Circulating Neutrophils That Provoke Multiple Organ Failure. Journal of Trauma-Injury Infection & Critical Care, 37, 881-887. https://doi.org/10.1097/00005373-199412000-00002
Robin, E., Guzy, R.D., Loor, G., Iwase, H., Waypa, G.B., Marks, J.D., Vanden Hoek, T.L. and Schumacker, P.T. (2007) Oxidant Stress during Simulated Ischemia Primes Cardiomyocytes for Cell Death during Reperfusion. The Journal of Biological Chemistry, 282, 19133-19143. https://doi.org/10.1074/jbc.M701917200
Gottardi, W., Hagleitner, M. and Nagl, M. (2005) N,N-Dichlorotaurine: Chemical and Bactericidal Properties. Archiv der Pharmazie, 338, 473-483. https://doi.org/10.1002/ardp.200500146