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Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Review Article

Hepatic Ischemia-reperfusion Injury: Protective Approaches and Treatment

Author(s): Kuldeep Singh*, Jeetendra Kumar Gupta, Shivendra Kumar, Anurag, Soumyadip Mukherjee and Aman Patel

Volume 17, 2024

Published on: 16 August, 2023

Article ID: e030823219400 Pages: 10

DOI: 10.2174/1874467217666230803114856



Ischemia and reperfusion damage to the liver is one of the major causes of hepatic dysfunction and liver failure after a liver transplant. The start of hepatic ischemia-reperfusion damage is linked to metabolic acidosis, Kupffer cells, neutrophils, excessive calcium, and changes in the permeability of the mitochondrial membrane. Hypoxia activates Kupffer cells, resulting in the production of reactive oxygen species (ROS). These ROS when accumulated, causes apoptosis and necrosis, as well as activate immune and inflammatory responses that involve many cells and signalling molecules. Numerous antioxidant compounds have been researched to lessen oxidative stress and thus serve as potential compounds to deal the ischemia-reperfusion damage. This article confers a deep understanding of the protective effects of some effective therapies, including hepatoprotective agents, attenuation of an increase in xanthine oxidase activity, and administration of antioxidants like N-acetylcysteine, superoxide dismutase (SOD), and ornithine.

Keywords: Ischemia-reperfusion, Antioxidant, Ornithine, N-acetylcysteine, Ischemia preconditioning, ROS.

Soares, ROS; Losada, DM; Jordani, MC; Évora, P Ischemia/reperfusion injury revisited: An overview of the latest pharmacological strategies. Int J Mol Sci., 2019, 20(20), 5034.
Wang, H.; Ma, S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am. J. Emerg. Med., 2008, 26(6), 711-715.
[] [PMID: 18606328]
Papadopoulos, D.; Siempis, T.; Theodorakou, E.; Tsoulfas, G. Hepatic ischemia and reperfusion injury and trauma: current concepts. Arch. Trauma Res., 2013, 2(2), 63-70.
[] [PMID: 24396796]
Varshney, V.; Goyal, A.; Gupta, J.K.; Yadav, H.N. Role of erythropoietin in ischemic postconditioning induced cardioprotection in hyperlipidemic rat heart. J. Indian Coll. Cardiol., 2017, 7(2), 72-77.
Li, S.; Hafeez, A.; Noorulla, F.; Geng, X.; Shao, G.; Ren, C.; Lu, G.; Zhao, H.; Ding, Y.; Ji, X. Preconditioning in neuroprotection: From hypoxia to ischemia. Prog. Neurobiol., 2017, 157, 79-91.
[] [PMID: 28110083]
Paschos, P.; Paletas, K. Non alcoholic fatty liver disease and metabolic syndrome. Int. J. Biol. Pharm. Allied Sci., 2021, 10(1 (SPECIAL ISSUE)), 9-19.
[] [PMID: 19240815]
Eipel, C.; Abshagen, K.; Vollmar, B. Regulation of hepatic blood flow: The hepatic arterial buffer response revisited. World J. Gastroenterol., 2010, 16(48), 6046-6057.
[] [PMID: 21182219]
Zhu, Y.; Dong, J.; Wang, W.L.; Li, M.X.; Long, Z.D.; Zhen, X.L.; Lv, Y. Ischemic preconditioning versus intermittent clamping of portal triad in liver resection: A meta-analysis of randomized controlled trials. Hepatol. Res., 2014, 44(8), 878-887.
[] [PMID: 23819558]
Chaudhury, S.; Seby, K.; Chakraborty, R. Prevalence of psychiatric and physical morbidity in an urban geriatric population. Indian J. Psychiatry, 2011, 53(2), 121-127.
[] [PMID: 21772643]
Rampes, S.; Ma, D. Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies. J. Biomed. Res., 2019, 33(4), 221-234.
[] [PMID: 32383437]
DeLeve, L.D. Liver sinusoidal endothelial cells and liver regeneration. J. Clin. Invest., 2013, 123(5), 1861-1866.
[] [PMID: 23635783]
Mao, X.; Cai, Y.; Chen, Y.; Wang, Y.; Jiang, X.; Ye, L.; Li, S. Novel targets and therapeutic strategies to protect against hepatic ischemia reperfusion injury. Front. Med., 2022, 8, 757336.
[] [PMID: 35059411]
Lushchak, V.I. Glutathione homeostasis and functions: Potential targets for medical interventions. J. Amino Acids, 2012, 2012, 1-26.
[] [PMID: 22500213]
Vieira Silva, S.; Freire, E.; Pessegueiro Miranda, H. Palliative care in end-stage liver disease patients awaiting liver transplantation. GE Port. J. Gastroenterol., 2020, 27(6), 417-428.
[] [PMID: 33251291]
Hirao, H; Nakamura, K; Kupiec-Weglinski, JW Liver ischaemia–reperfusion injury: A new understanding of the role of innate immunity. Nat Rev Gastroenterol Hepatol, 2022, 19(4), 239-256.
Wu, M.Y.; Yiang, G.T.; Liao, W.T.; Tsai, A.P.Y.; Cheng, Y.L.; Cheng, P.W.; Li, C.Y.; Li, C.J. Current mechanistic concepts in ischemia and reperfusion injury. Cell. Physiol. Biochem., 2018, 46(4), 1650-1667.
[] [PMID: 29694958]
Petrenko, A.; Carnevale, M.; Somov, A.; Osorio, J.; Rodríguez, J.; Guibert, E.; Fuller, B.; Froghi, F. Organ Preservation into the 2020s: The Era of Dynamic Intervention. Transfus. Med. Hemother., 2019, 46(3), 151-172.
[] [PMID: 31244584]
Bochimoto, H.; Ishihara, Y.; Mohd Zin, N.K.; Iwata, H.; Kondoh, D.; Obara, H.; Matsuno, N. Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death. World J. Gastroenterol., 2022, 28(19), 2100-2111.
[] [PMID: 35664031]
Pulakat, L.; Sumners, C. Angiotensin Type 2 receptors: Painful, or not? Front. Pharmacol., 2020, 11, 571994.
[] [PMID: 33424587]
Sastre, J.; Serviddio, G.; Pereda, J.; Minana, J.B.; Arduini, A.; Vendemiale, G.; Poli, G.; Pallardo, F.V.; Vina, J. Mitochondrial function in liver disease. Front. Biosci., 2007, 12(1), 1200-1209.
[] [PMID: 17127373]
Abu-Amara, M.; Yang, S.Y.; Tapuria, N.; Fuller, B.; Davidson, B.; Seifalian, A. Liver ischemia/reperfusion injury: Processes in inflammatory networks-A review. Liver Transpl., 2010, 16(9), 1016-1032.
[] [PMID: 20818739]
Brass, C.A.; Roberts, T.G. Hepatic free radical production after cold storage: Kupffer cell-dependent and -independent mechanisms in rats. Gastroenterology, 1995, 108(4), 1167-1175.
[] [PMID: 7698585]
Kanoria, S.; Glantzounis, G.; Quaglia, A.; Dinesh, S.; Fusai, G.; Davidson, B.R.; Seifalian, A.M. Remote preconditioning improves hepatic oxygenation after ischaemia reperfusion injury. Transpl. Int., 2012, 25(7), 783-791.
[] [PMID: 22533545]
Jaeschke, H. Reactive oxygen and ischemia/reperfusion injury of the liver. Chem. Biol. Interact., 1991, 79(2), 115-136.
[] [PMID: 1884426]
Rüdiger, H.A.; Clavien, P.A. Tumor necrosis factor α, but not Fas, mediates hepatocellular apoptosis in the murine ischemic liver. Gastroenterology, 2002, 122(1), 202-210.
[] [PMID: 11781294]
Rauen, U.; Polzar, B.; Stephan, H.; Mannherz, H.G.; De Groot, H. Cold‐induced apoptosis in cultured hepatocytes and liver endothelial cells: Mediation by reactive oxygen species. FASEB J., 1999, 13(1), 155-168.
[] [PMID: 9872940]
Giakoustidis, D.; Papageorgiou, G.; Iliadis, S.; Kontos, N.; Kostopoulou, E.; Papachrestou, A.; Tsantilas, D.; Spyridis, C.; Takoudas, D.; Botsoglou, N.; Dimitriadou, A.; Giakoustidis, E. Intramuscular administration of very high dose of alpha-tocopherol protects liver from severe ischemia/reperfusion injury. World J. Surg., 2002, 26(7), 872-877.
[] [PMID: 11960213]
Montalvo-Jave, E.E.; Escalante-Tattersfield, T.; Ortega-Salgado, J.A.; Piña, E.; Geller, D.A. Factors in the pathophysiology of the liver ischemia-reperfusion injury. J. Surg. Res., 2008, 147(1), 153-159.
[] [PMID: 17707862]
Boury, N.M.; Czuprynski, C.J. Listeria monocytogenes infection increases neutrophil adhesion and damage to a murine hepatocyte cell line in vitro. Immunol. Lett., 1995, 46(1-2), 111-116.
[] [PMID: 7590905]
Peralta, C.; Fernández, L.; Panés, J.; Prats, N.; Sans, M.; Piqué, J.M.; Gelpí, E.; Roselló-Catafau, J. Preconditioning protects against systemic disorders associated with hepatic ischemia-reperfusion through blockade of tumor necrosis factor–induced P-selectin up-regulation in the rat. Hepatology, 2001, 33(1), 100-113.
[] [PMID: 11124826]
Schwabe, R.F.; Brenner, D.A. Mechanisms of Liver Injury. I. TNF-α-induced liver injury: Role of IKK, JNK, and ROS pathways. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290(4), G583-G589.
[] [PMID: 16537970]
Teodoro, JS; Da Silva, RT; Machado, IF; Panisello-Roselló, A; Roselló-Catafau, J; Rolo, AP Shaping of hepatic ischemia/reperfusion events: The crucial role of mitochondria. Cells, 2022, 11(4), 688.
Schewe, J.; Makeschin, M.C.; Khandoga, A.; Zhang, J.; Mayr, D.; Rothenfußer, S.; Schnurr, M.; Gerbes, A.L.; Steib, C.J. To protect fatty livers from ischemia reperfusion injury: Role of ischemic postconditioning. Dig. Dis. Sci., 2021, 66(4), 1349-1359.
[] [PMID: 32451758]
Jin, S.; Dai, C.L. Hepatic blood inflow occlusion without hemihepatic artery control in treatment of hepatocellular carcinoma. World J. Gastroenterol., 2010, 16(46), 5895-5900.
[] [PMID: 21155013]
Jaramillo, S.; Montane-Muntane, M.; Gambus, P.L.; Capitan, D.; Navarro-Ripoll, R.; Blasi, A. Perioperative blood loss: Estimation of blood volume loss or haemoglobin mass loss? Blood Transfus., 2020, 18(1), 20-29.
[] [PMID: 31855150]
Singh, K.; Kumar Gupta, J.; Singh, K.; Kumar, S. Protective effects of ornithine on hepatic ischemia-reperfusion injury. Int J Gastroenterol Hepatol Dis, 2023, 2(Apr), e070423215558.
Chouillard, E.K.; Gumbs, A.A.; Cherqui, D. Vascular clamping in liver surgery: Physiology, indications and techniques. Ann. Surg. Innov. Res., 2010, 4(1), 2.
[] [PMID: 20346153]
Granfeldt, A.; Lefer, D.J.; Vinten-Johansen, J. Protective ischaemia in patients: Preconditioning and postconditioning. Cardiovasc. Res., 2009, 83(2), 234-246.
[] [PMID: 19398470]
Sugi, M.D.; Joshi, G.; Maddu, K.K.; Dahiya, N.; Menias, C.O. Imaging of renal transplant complications throughout the life of the allograft: comprehensive multimodality review. Radiographics, 2019, 39(5), 1327-1355.
[] [PMID: 31498742]
Azoulay, D.; Eshkenazy, R.; Andreani, P.; Castaing, D.; Adam, R.; Ichai, P.; Naili, S.; Vinet, E.; Saliba, F.; Lemoine, A.; Gillon, M.C.; Bismuth, H. In situ hypothermic perfusion of the liver versus standard total vascular exclusion for complex liver resection. Ann. Surg., 2005, 241(2), 277-285.
[] [PMID: 15650638]
Zhang, H.; Yan, Q.; Wang, X.; Chen, X.; Chen, Y.; Du, J.; Chen, L. The role of mitochondria in liver ischemia-reperfusion injury: From aspects of mitochondrial oxidative stress, mitochondrial fission, mitochondrial membrane permeable transport pore formation, mitophagy, and mitochondria-related protective measures. Oxid. Med. Cell. Longev., 2021, 2021, 1-12.
[] [PMID: 34285766]
Yellon, D.M.; Downey, J.M. Preconditioning the myocardium: From cellular physiology to clinical cardiology. Physiol. Rev., 2003, 83(4), 1113-1151.
[] [PMID: 14506302]
Eren, E.A.; Latchana, N.; Beal, E.; Hayes, D., Jr; Whitson, B.; Black, S.M. Donations after circulatory death in liver transplant. Exp. Clin. Transplant., 2016, 14(5), 463-470.
[] [PMID: 27733105]
Tolboom, H.; Pouw, R.E.; Izamis, M.L.; Milwid, J.M.; Sharma, N.; Soto-Gutierrez, A.; Nahmias, Y.; Uygun, K.; Berthiaume, F.; Yarmush, M.L. Recovery of warm ischemic rat liver grafts by normothermic extracorporeal perfusion. Transplantation, 2009, 87(2), 170-177.
[] [PMID: 19155970]
Azoulay, D.; Del Gaudio, M.; Andreani, P.; Ichai, P.; Sebag, M.; Adam, R.; Scatton, O.; Min, B.Y.; Delvard, V.; Lemoine, A.; Bismuth, H.; Castaing, D. Effects of 10 minutes of ischemic preconditioning of the cadaveric liver on the graft’s preservation and function: The ying and the yang. Ann. Surg., 2005, 242(1), 133-139.
[] [PMID: 15973111]
Dong, M.H.; Bettencourt, R.; Brenner, D.A.; Barrett-Connor, E.; Loomba, R. Serum levels of alanine aminotransferase decrease with age in longitudinal analysis. Clin. Gastroenterol. Hepatol., 2012, 10(3), 285-290.e1.
[] [PMID: 22020064]
Hausenloy, D.J.; Barrabes, J.A.; Bøtker, H.E.; Davidson, S.M.; Di Lisa, F.; Downey, J.; Engstrom, T.; Ferdinandy, P.; Carbrera-Fuentes, H.A.; Heusch, G.; Ibanez, B.; Iliodromitis, E.K.; Inserte, J.; Jennings, R.; Kalia, N.; Kharbanda, R.; Lecour, S.; Marber, M.; Miura, T.; Ovize, M.; Perez-Pinzon, M.A.; Piper, H.M.; Przyklenk, K.; Schmidt, M.R.; Redington, A.; Ruiz-Meana, M.; Vilahur, G.; Vinten-Johansen, J.; Yellon, D.M.; Garcia-Dorado, D. Ischaemic conditioning and targeting reperfusion injury: A 30 year voyage of discovery. Basic Res. Cardiol., 2016, 111(6), 70.
[] [PMID: 27766474]
Llacuna, L.; Marí, M.; Lluis, J.M.; García-Ruiz, C.; Fernández-Checa, J.C.; Morales, A. Reactive oxygen species mediate liver injury through parenchymal nuclear factor-kappaB inactivation in prolonged ischemia/reperfusion. Am. J. Pathol., 2009, 174(5), 1776-1785.
[] [PMID: 19349371]
Li, Y; Palmer, A; Lupu, L; Huber-Lang, M Inflammatory response to the ischaemia–reperfusion insult in the liver after major tissue trauma. Eur J Trauma Emerg Surg., 2022, 48(6), 1-14.
Sakai, N.; Van Sweringen, H.L.; Schuster, R.; Blanchard, J.; Burns, J.M.; Tevar, A.D.; Edwards, M.J.; Lentsch, A.B. Receptor activator of nuclear factor-κB ligand (RANKL) protects against hepatic ischemia/reperfusion injury in mice. Hepatology, 2012, 55(3), 888-897.
[] [PMID: 22031462]
Yoon, SH; Kang, HB; Kim, J; Yoo, K; Han, SJ Diminazene aceturate attenuates hepatic ischemia/reperfusion injury in mice. Sci Rep., 2022, 12(1), 18158.
Tang, Y.; Wang, T.; Ju, W.; Li, F.; Zhang, Q.; Chen, Z.; Gong, J.; Zhao, Q.; Wang, D.; Chen, M.; Guo, Z.; He, X. Ischemic-free liver transplantation reduces the recurrence of hepatocellular carcinoma after liver transplantation. Front. Oncol., 2021, 11, 773535.
[] [PMID: 34966679]
Michielsen, P.P.; Francque, S.M.; van Dongen, J.L. Viral hepatitis and hepatocellular carcinoma. World J. Surg. Oncol., 2005, 3(1), 27.
[] [PMID: 15907199]
Bae, H.B. Volatile anesthetics and ischemia-reperfusion injury. Korean J. Anesthesiol., 2015, 68(3), 211-212.
[] [PMID: 26045921]
Cottart, C.H.; Do, L.; Blanc, M.C.; Vaubourdolle, M.; Descamps, G.; Durand, D.; Galen, F.X.; Clot, J.P. Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat. Hepatology, 1999, 29(3), 809-813.
[] [PMID: 10051483]
Vollmar, B.; Menger, M.D. The hepatic microcirculation: Mechanistic contributions and therapeutic targets in liver injury and repair. Physiol. Rev., 2009, 89(4), 1269-1339.
[] [PMID: 19789382]
Reynaert, H.; Thompson, M.G.; Thomas, T.; Geerts, A. Hepatic stellate cells: Role in microcirculation and pathophysiology of portal hypertension. Gut, 2002, 50(4), 571-581.
[] [PMID: 11889082]
Torres Crigna, A.; Link, B.; Samec, M.; Giordano, F.A.; Kubatka, P.; Golubnitschaja, O. Endothelin-1 axes in the framework of predictive, preventive and personalised (3P) medicine. EPMA J., 2021, 12(3), 265-305.
[] [PMID: 34367381]
Singh, K.; Kumar Gupta, J.; Singh, K.; Kumar, S. The efficacy of current medications and biomarkers in hepatic ischemia-reperfusion damage. Int J Gastroenterol Hepatol Dis, 2023, 2(Apr)
Dar, W.A.; Sullivan, E.; Bynon, J.S.; Eltzschig, H.; Ju, C. Ischaemia reperfusion injury in liver transplantation: Cellular and molecular mechanisms. Liver Int., 2019, 39(5), 788-801.
[] [PMID: 30843314]
Guan, L.Y.; Fu, P.Y.; Li, P.D.; Li, Z.N.; Liu, H.Y.; Xin, M.G.; Li, W. Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide. World J. Gastrointest. Surg., 2014, 6(7), 122-128.
[] [PMID: 25068009]
Saidi, R.F.; Chang, J.; Verb, S.; Brooks, S.; Nalbantoglu, I.; Adsay, V.; Jacobs, M.J. The effect of methylprednisolone on warm ischemia-reperfusion injury in the liver. Am. J. Surg., 2007, 193(3), 345-348.
[] [PMID: 17320532]
Ocuin, L.M.; Zeng, S.; Cavnar, M.J.; Sorenson, E.C.; Bamboat, Z.M.; Greer, J.B.; Kim, T.S.; Popow, R.; DeMatteo, R.P. Nilotinib protects the murine liver from ischemia/reperfusion injury. J. Hepatol., 2012, 57(4), 766-773.
[] [PMID: 22641092]
Gao, F.; Qiu, X.; Wang, K.; Shao, C.; Jin, W.; Zhang, Z.; Xu, X. Targeting the hepatic microenvironment to improve ischemia/reperfusion injury: new insights into the immune and metabolic compartments. Aging Dis., 2022, 13(4), 1196-1214.
[] [PMID: 35855339]
Olthof, P.B.; van Golen, R.F.; Meijer, B.; van Beek, A.A.; Bennink, R.J.; Verheij, J.; van Gulik, T.M.; Heger, M. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(2), 375-385.
[] [PMID: 27989959]
Li, J; Li, RJ; Lv, GY; Liu, HQ The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci, 2015, 19(11), 2036-2047.
Bhattacharyya, A.; Chattopadhyay, R.; Mitra, S.; Crowe, S.E. Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol. Rev., 2014, 94(2), 329-354.
[] [PMID: 24692350]
Granger, D.N.; Kvietys, P.R. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol., 2015, 6, 524-551.
[] [PMID: 26484802]
Chaves Cayuela, N.; Kiyomi Koike, M.; Jacysyn, J.; Rasslan, R.; Azevedo Cerqueira, A.; Pereira Costa, S.; Picanço Diniz-Júnior, J.; Massazo Utiyama, E.; Frasson de Souza Montero, E. N-acetylcysteine reduced ischemia and reperfusion damage associated with steatohepatitis in mice. Int. J. Mol. Sci., 2020, 21(11), 4106.
[] [PMID: 32526845]
Schauer, R.J.; Gerbes, A.L.; Vonier, D.; Meissner, H.; Michl, P.; Leiderer, R.; Schildberg, F.W.; Messmer, K.; Bilzer, M. Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia. Ann. Surg., 2004, 239(2), 220-231.
[] [PMID: 14745330]
Younus, H. Therapeutic potentials of superoxide dismutase. Int J Health Sci, 2018, 12(3), 88-93.
Reddy, M.K.; Labhasetwar, V. Nanoparticle‐mediated delivery of superoxide dismutase to the brain: An effective strategy to reduce ischemia‐reperfusion injury. FASEB J., 2009, 23(5), 1384-1395.
[] [PMID: 19124559]
Rinaldi Tosi, M.E.; Bocanegra, V.; Manucha, W.; Gil Lorenzo, A.; Vallés, P.G. The Nrf2–Keap1 cellular defense pathway and heat shock protein 70 (Hsp70) response. Role in protection against oxidative stress in early neonatal unilateral ureteral obstruction (UUO). Cell Stress Chaperones, 2011, 16(1), 57-68.
[] [PMID: 20734248]
Constantin, M.; Choi, A.J.S.; Cloonan, S.M.; Ryter, S.W. Therapeutic potential of heme oxygenase-1/carbon monoxide in lung disease. Int. J. Hypertens., 2012, 2012, 1-19.
[] [PMID: 22518295]
Wu, H.H.; Huang, C.C.; Chang, C.P.; Lin, M.T.; Niu, K.C.; Tian, Y.F. Heat shock Protein 70 (HSP70) reduces hepatic inflammatory and oxidative damage in a rat model of liver ischemia/reperfusion injury with hyperbaric oxygen preconditioning. Med. Sci. Monit., 2018, 24, 8096-8104.
[] [PMID: 30417859]
Hoglen, N.C.; Anselmo, D.M.; Katori, M.; Kaldas, M.; Shen, X.D.; Valentino, K.L.; Lassman, C.; Busuttil, R.W.; Kupiec-Weglinski, J.W.; Farmer, D.G. A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia. Liver Transpl., 2007, 13(3), 361-366.
[] [PMID: 17318854]
Jeon, B.R.; Yeom, D.H.; Lee, S.M. Protective effect of allopurinol on hepatic energy metabolism in ischemic and reperfused rat liver. Shock, 2001, 15(2), 112-117.
[] [PMID: 11220638]
Guo, J.; Zhang, T.; Gu, J.; Cai, K.; Deng, X.; Chen, K.; Huang, K.; Wang, G.; Li, H.; Wang, J. Oleic acid protects against hepatic ischemia and reperfusion injury in mice by inhibiting AKT/mTOR pathways. Oxid. Med. Cell. Longev., 2019, 2019, 1-18.
[] [PMID: 31915509]
Alfonso-Prieto, M.; Biarnés, X.; Vidossich, P.; Rovira, C. The molecular mechanism of the catalase reaction. J. Am. Chem. Soc., 2009, 131(33), 11751-11761.
[] [PMID: 19653683]
Matsumoto, H.; Silverton, S.F.; Debolt, K.; Shapiro, I.M. Superoxide dismutase and catalase activities in the growth cartilage: Relationship between oxidoreductase activity and chondrocyte maturation. J. Bone Miner. Res., 1991, 6(6), 569-574.
[] [PMID: 1887819]
Nita, M.; Grzybowski, A. The role of the reactive oxygen species and oxidative stress in the pathomechanism of the age-related ocular diseases and other pathologies of the anterior and posterior eye segments in adults. Oxid. Med. Cell. Longev., 2016, 2016, 1-23.
[] [PMID: 26881021]
Kaspar, J.W.; Niture, S.K.; Jaiswal, A.K. Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic. Biol. Med., 2009, 47(9), 1304-1309.
[] [PMID: 19666107]
Sahebkar, A.; Cicero, A.F.G.; Simental-Mendía, L.E.; Aggarwal, B.B.; Gupta, S.C. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol. Res., 2016, 107, 234-242.
[] [PMID: 27025786]
Zaki, H.F.; Abdelsalam, R.M. Vinpocetine protects liver against ischemia–reperfusion injury. Can. J. Physiol. Pharmacol., 2013, 91(12), 1064-1070.
[] [PMID: 24289077]
Lin, C.M.; Lee, J.F.; Chiang, L.L.; Chen, C.F.; Wang, D.; Su, C.L. The protective effect of curcumin on ischemia-reperfusion-induced liver injury. Transplant. Proc., 2012, 44(4), 974-977.
[] [PMID: 22564600]
Truong, V.L.; Jun, M.; Jeong, W.S. Role of resveratrol in regulation of cellular defense systems against oxidative stress. Biofactors, 2018, 44(1), 36-49.
[] [PMID: 29193412]
Wang, Y.; Sun, X.; Han, X.; Sun, J.; Li, L.; Zhang, D.; Sun, G. Resveratrol improves hepatic ischemia-reperfusion injury by inhibiting neutrophils via the ERK signaling pathway. Biomed. Pharmacother., 2023, 160, 114358.
[] [PMID: 36739762]
Dusabimana, T.; Kim, S.R.; Kim, H.J.; Park, S.W.; Kim, H. Nobiletin ameliorates hepatic ischemia and reperfusion injury through the activation of SIRT-1/FOXO3a-mediated autophagy and mitochondrial biogenesis. Exp. Mol. Med., 2019, 51(4), 1-16.
[] [PMID: 31028246]
Chen, J.H.; Tipoe, G.L.; Liong, E.C.; So, H.S.H.; Leung, K.M.; Tom, W.M.; Fung, P.C.W.; Nanji, A.A. Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide–derived prooxidants. Am. J. Clin. Nutr., 2004, 80(3), 742-751.
[] [PMID: 15321817]
Zhong, Z.; Froh, M.; Connor, H.D.; Li, X.; Conzelmann, L.O.; Mason, R.P.; Lemasters, J.J.; Thurman, R.G. Prevention of hepatic ischemia-reperfusion injury by green tea extract. Am. J. Physiol. Gastrointest. Liver Physiol., 2002, 283(4), G957-G964.
[] [PMID: 12223356]
Zhang, X.G.; Xu, P.; Liu, Q.; Yu, C.H.; Zhang, Y.; Chen, S.H.; Li, Y.M. Effect of tea polyphenol on cytokine gene expression in rats with alcoholic liver disease. Hepatobiliary Pancreat. Dis. Int., 2006, 5(2), 268-272.
[PMID: 16698589]
Fan, S.; Zhang, C.; Luo, T.; Wang, J.; Tang, Y.; Chen, Z.; Yu, L. Limonin: A review of its pharmacology, toxicity, and pharmacokinetics. Molecules, 2019, 24(20), 3679.
[] [PMID: 31614806]
Mahmoud, M.F.; Gamal, S.; El-Fayoumi, H.M. Limonin attenuates hepatocellular injury following liver ischemia and reperfusion in rats via toll-like receptor dependent pathway. Eur. J. Pharmacol., 2014, 740, 676-682.
[] [PMID: 24967531]
Niu, X.; Zhang, Y.; Cheng, M.; Yin, N.; Wu, Y.; Shi, W.; Yang, Y.; Zhu, L.; Huang, C.; Li, J. 7-O-(2- (Propylamino)-2-oxoethyl) hesperetin attenuates inflammation and protects against alcoholic liver injury by NLRP12. Int. Immunopharmacol., 2022, 110, 109006.
[] [PMID: 35792270]
Puthanveetil, P.; Kong, X.; Bräse, S.; Voros, G.; Peer, W.A. Transcriptome analysis of two structurally related flavonoids; Apigenin and Chrysin revealed hypocholesterolemic and ketogenic effects in mouse embryonic fibroblasts. Eur. J. Pharmacol., 2021, 893, 173804.
[] [PMID: 33347826]
Lin, J.; Tian, J.; Shu, C.; Cheng, Z.; Liu, Y.; Wang, W.; Liu, R.; Li, B.; Wang, Y. Malvidin-3-galactoside from blueberry suppresses the growth and metastasis potential of hepatocellular carcinoma cell Huh-7 by regulating apoptosis and metastases pathways. Food Sci. Hum. Wellness, 2020, 9(2), 136-145.
Nassef, N.A. Quercetin improves platelet function and ultrastructure in cholestatic liver injury in rats: Role of ORAI1 gene expression. Gene Rep., 2019, 17, 100485.
Yu, Z.; Yang, L.; Deng, S.; Liang, M. Daidzein ameliorates LPS-induced hepatocyte injury by inhibiting inflammation and oxidative stress. Eur. J. Pharmacol., 2020, 885, 173399.
[] [PMID: 32712091]
Wu, H.; Xie, Y.; Xu, Y.; Hu, Z.; Wan, X.; Huang, H.; Huang, D. Protective effect of Epicatechin on APAP-induced acute liver injury of mice through anti-inflammation and apoptosis inhibition. Nat. Prod. Res., 2020, 34(6), 855-858.
[] [PMID: 30394110]
Patel, R.P.; Lang, J.D.; Smith, A.B.; Crawford, J.H. Redox therapeutics in hepatic ischemia reperfusion injury. World J. Hepatol., 2014, 6(1), 1-8.
[] [PMID: 24653789]
Ingram, H; Dogan, M; Eason, JD; Kuscu, C; Kuscu, C MicroRNAs: Novel targets in hepatic ischemia–reperfusion injury. Biomedicines, 2022, 10(4), 791.
Kensler, T.W.; Wakabayashi, N.; Biswal, S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol., 2007, 47(1), 89-116.
[] [PMID: 16968214]
Klune, J.R.; Tsung, A. Molecular biology of liver ischemia/reperfusion injury: established mechanisms and recent advancements. Surg. Clin. North Am., 2010, 90(4), 665-677.
[] [PMID: 20637940]
Yang, J.; Marden, J.J.; Fan, C.; Sanlioglu, S.; Weiss, R.M.; Ritchie, T.C.; Davisson, R.L.; Engelhardt, J.F. Genetic redox preconditioning differentially modulates AP-1 and NFκB responses following cardiac ischemia/reperfusion injury and protects against necrosis and apoptosis. Mol. Ther., 2003, 7(3), 341-353.
[] [PMID: 12668130]
Cesaratto, L.; Vascotto, C.; D’Ambrosio, C.; Scaloni, A.; Baccarani, U.; Paron, I.; Damante, G.; Calligaris, S.; Quadrifoglio, F.; Tiribelli, C.; Tell, G. Overoxidation of peroxiredoxins as an immediate and sensitive marker of oxidative stress in HepG2 cells and its application to the redox effects induced by ischemia/reperfusion in human liver. Free Radic. Res., 2005, 39(3), 255-268.
[] [PMID: 15788230]
Robinson, R.T.; Wang, J.; Cripps, J.G.; Milks, M.W.; English, K.A.; Pearson, T.A.; Gorham, J.D. End-organ damage in a mouse model of fulminant liver inflammation requires CD4+ T cell production of IFN-gamma but is independent of Fas. J. Immunol., 2009, 182(5), 3278-3284.
[] [PMID: 19234226]
Kuyvenhoven, J.P.; Verspaget, H.W.; Gao, Q.; Ringers, J.; Smit, V.T.H.B.M.; Lamers, C.B.H.W.; van Hoek, B. Assessment of serum matrix metalloproteinases MMP-2 and MMP-9 after human liver transplantation: increased serum MMP-9 level in acute rejection. Transplantation, 2004, 77(11), 1646-1652.
[] [PMID: 15201662]
Duarte, S; Baber, J; Fujii, T; Coito, AJ Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biol, 2015, 44-46, 147-156.
Jaeschke, H.; Woolbright, B.L. Current strategies to minimize hepatic ischemia–reperfusion injury by targeting reactive oxygen species. Transplant. Rev., 2012, 26(2), 103-114.
[] [PMID: 22459037]
Kalimeris, K.; Briassoulis, P.; Ntzouvani, A.; Nomikos, T.; Papaparaskeva, K.; Politi, A.; Batistaki, C.; Kostopanagiotou, G. N-acetylcysteine ameliorates liver injury in a rat model of intestinal ischemia reperfusion. J. Surg. Res., 2016, 206(2), 263-272.
[] [PMID: 27884318]
Sözen, S.; Kisakürek, M.; Yildiz, F.; Gönültaş, M.; Dinçel, A.S. The effects of glutamine on hepatic ischemia reperfusion injury in rats. Hippokratia, 2011, 15(2), 161-166.
[PMID: 22110300]
Sidhu, S.S. L-ornithine L-aspartate is effective and safe for the treatment of hepatic encephalopathy in cirrhosis. J. Clin. Exp. Hepatol., 2018, 8(3), 219-221.
[] [PMID: 30302036]
Vanisree, A.J.; Shyamaladevi, C.S. The effect of N-acetylcysteine in combination with vitamin C on the activity of ornithine decarboxylase of lung carcinoma cells — In vitro. Life Sci., 2006, 79(7), 654-659.
[] [PMID: 16574159]
Caldwell, R.W.; Rodriguez, P.C.; Toque, H.A.; Narayanan, S.P.; Caldwell, R.B. Arginase: A multifaceted enzyme important in health and disease. Physiol. Rev., 2018, 98(2), 641-665.
[] [PMID: 29412048]

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