Abstract
Ischemia/reperfusion injury (IRI) is a key determining agent in the pathophysiology of clinical organ dysfunction. It is characterized by an aseptic local inflammatory reaction due to a decrease in blood supply, hence deprivation of dependent oxygen and nutrients. In instances of liver transplantation, this injury may have irreversible implications, resulting in eventual organ rejection. The deterioration associated with IRI is affected by the hepatic health status and various factors such as alterations in metabolism, oxidative stress, and pro-inflammatory cytokines. The primary cause of inflammation is the initial immune response of pro-inflammatory cytokines, while Kupffer cells (KFCs) and neutrophil-produced chemokines also play a significant role. Upon reperfusion, the activation of inflammatory responses can elicit further cellular damage and organ dysfunction. This review discusses the interplay between chemokines, pro-inflammatory cytokines, and other inflammatory mediators that contribute to the damage to hepatocytes and liver failure in rats following IR. Furthermore, it delves into the impact of anti-inflammatory therapies in safeguarding against liver failure and hepatocellular damage in rats following IR. This review investigates the correlation between cytokine factors and liver dysfunction via examining databases, such as PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate.
Graphical Abstract
The abstract diagram illustrates the pro-inflammatory cytokines and NF-κB as primary target therapies for cytoprotecting activity versus ischemia/reperfusion injury of the liver.
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Data availability
No datasets were generated or analysed during the current study.
Abbreviations
- ATP:
-
Adenosine triphosphate
- ATRA:
-
All-trans retinoic acid
- COX-2:
-
Cyclooxygenase-2
- EKB:
-
Egyptian knowledge bank
- ENA-78:
-
Epithelial neutrophil-activating protein-78
- EPO:
-
Erythropoietin
- Gdcl3:
-
Gadolinium chloride
- IFN:
-
Interferon
- IκB:
-
Inhibitor of Kapp B
- IL:
-
Interleukin
- iNOS:
-
Inducible nitric oxide synthase
- IRI:
-
Ischemia/reperfusion injury
- JNK:
-
Jun N-terminal kinase
- KFCs:
-
Kuppfer cells
- LPS:
-
Lipopolysaccharide
- L-THP:
-
Levo-tetrahydropalmatine
- MAPK:
-
Mitogen-activated protein kinase
- MMP:
-
Matrix metalloproteinase
- MTA:
-
5′-Methylthioadenosine
- NAC:
-
N-acetyl cysteine
- NF-κB:
-
Nuclear factor kappa B
- ROS:
-
Reactive oxygen species
- RCTs:
-
Randomized controlled trials
- TGF-β:
-
Tumor growth factor β
- TLR:
-
Toll-like receptors
- VEGF:
-
Vascular endothelial growth factor
References
Abouzed DE, Mahmoud HM, Murad A, Hemada RH (2023) Empagliflozin mitigates ischemia/reperfusion-induced liver injury in rats: modulation of NF-κB, SMAD-4, VEGF, and fibrinogen protein expressions. Bulletin of Pharmaceutical Sciences Assiut University
Ahmed S, EL-Sayed MM, Kandeil MA, Khalaf MM (2022) Empagliflozin attenuates neurodegeneration through antioxidant, anti-inflammatory, and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinson’s disease in rats. Saudi Pharm J 30(6):863–873. https://doi.org/10.1016/j.jsps.2022.03.005
Albers E (2009) Metabolic characteristics and importance of the universal methionine salvage pathway recycling methionine from 5′-methylthioadenosine. IUBMB Life 61(12):1132–1142. https://doi.org/10.1002/iub.278
Ambigaipalan P, de Camargo AC, Shahidi F (2016) Phenolic compounds of pomegranate byproducts (outer skin, mesocarp, divider membrane) and their antioxidant activities. J Agric Food Chem 64(34):6584–6604. https://doi.org/10.1021/acs.jafc.6b02950
Anstee QM, Day CP (2012) S-adenosylmethionine (SAMe) therapy in liver disease: a review of current evidence and clinical utility. J Hepatol 57(5):1097–1109. https://doi.org/10.1016/j.jhep.2012.04.041
Atzeni F, Doria A, Carrabba M et al (2007) (2007) Potential target of infliximab in autoimmune and inflammatory diseases. Autoimmun Rev 6(8):529–536. https://doi.org/10.1016/j.autrev.2007.03.009
Bektas S, Karakaya K, Can M et al (2016) The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury. Kaohsiung J Med Sci 32:339–347. https://doi.org/10.1016/j.kjms.2016.05.005
Beshay E, Croze F, Prudhomme GJ (2001) The phosphodiesterase inhibitors pentoxifylline and rolipram suppress macrophage activation and nitric oxide production in vitro and in vivo. Clin Immunol 98(2):272–279. https://doi.org/10.1006/clim.2000.4964
Bochořáková H, Paulová H, Slanina J et al (2003) Main flavonoids in the root of Scutellaria baicalensis cultivated in Europe and their comparative antiradical properties. Phytother Res 17(6):640–644. https://doi.org/10.1002/ptr.1216
Boros P, Tarcsafalvi A, Wang L et al (2001) Intrahepatic expression and release of vascular endothelial growth factor following orthotopic liver transplantation in the rat. Transplantation 72(5):805–811. https://doi.org/10.1097/00007890-200109150-00011
Cannistrà M, Ruggiero M, Zullo A et al (2016) Hepatic ischemia reperfusion injury: a systematic review of literature and the role of current drugs and biomarkers. Int J Surg 33:S57–S70. https://doi.org/10.1016/j.ijsu.2016.05.050
Casillas-Ramirez A, Amine-Zaouali M, Massip-Salcedo M et al (2008) Inhibition of angiotensin II action protects rat steatotic livers against ischemia-reperfusion injury. Crit Care Med 36:1256–1266. https://doi.org/10.1097/ccm.0b013e31816a023c
Chen D, Frezza M, Schmitt S et al (2011) Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Target 11(3):239–253. https://doi.org/10.2174/156800911794519752
Chen RX, Jiang WJ, Liu SC et al (2023) Apolipoprotein A-1 protected hepatic ischaemia–reperfusion injury through suppressing macrophage pyroptosis via TLR4–NF-κB pathway. Liver Int 43(1):234–248. https://doi.org/10.1111/liv.15448
Chu H, Jin G, Friedman E et al (2008) Recent development in studies of tetrahydroprotoberberines: mechanism in antinociception and drug addiction. Cell Mol Neurobiol 28:491–499. https://doi.org/10.1007/s10571-007-9179-4
Chullo G, Panisello-Rosello A, Marquez N et al (2024) Focusing on ischemic reperfusion injury in the new era of dynamic machine perfusion in liver transplantation. Int J Mol Sci 25:1117. https://doi.org/10.3390/ijms25021117
Czigany Z, Lurje I, Schmelzle M et al (2020) Ischemia-reperfusion injury in marginal liver grafts and the role of hypothermic machine perfusion: molecular mechanisms and clinical implications. J Clin Med 9:846. https://doi.org/10.3390/jcm9030846
Dar WA, Sullivan E, Bynon JS et al (2019) Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms. Liv Int 39:788–801. https://doi.org/10.1111/liv.14091
Datta G, Fuller BJ, Davidson BR (2013) Molecular mechanisms of liver ischemia reperfusion injury: insights from transgenic knockout models. Wor J Gast WJG 19:1683. https://doi.org/10.3748/wjg.v19.i11.1683
Diao W, Lu L, Li S et al (2017) MicroRNA-125b-5p modulates the inflammatory state of macrophages via targeting B7–H4. Biochem Biophys Res Commun 491(4):912–918. https://doi.org/10.1016/j.bbrc.2017.07.135
Ding J, Wenjuan Y, Jiang Y et al (2022) Cordycepin protects against hepatic ischemia/reperfusion injury via inhibiting MAPK/NF-kB pathway. Mediators Inflamm 5676256. https://doi.org/10.1155/2022/5676256
Durgun C, Aşir F (2022) Effect of ellagic acid on damage caused by hepatic ischemia reperfusion in rats. Eur Rev Med Pharmacol Sci 26(22). https://doi.org/10.26355/eurrev_202211_30352
Dutkowski P, Linecker M, DeOliveira ML et al (2015) Challenges to liver transplantation and strategies to improve outcomes. Gastroenterology 148:307–323. https://doi.org/10.1053/j.gastro.2014.08.045
Erturk E, Topaloglu S, Dohman D et al (2014) The comparison of the effects of sevoflurane inhalation anesthesia and intravenous propofol anesthesia on oxidative stress in one lung ventilation. BioMed Res Int. https://doi.org/10.1155/2014/360936
Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1(1):27–31. https://doi.org/10.1038/nm0195-27
Franchello A, Gilbo N, David E et al (2009) Ischemic preconditioning (IP) of the liver as a safe and protective technique against ischemia/reperfusion injury (IRI). Am J Transplant 9:1629–1639. https://doi.org/10.1111/j.1600-6143.2009.02680.x
Gao Y, Li ZT, Jin L et al (2021) Melatonin attenuates hepatic ischemia-reperfusion injury in rats by inhibiting NF-κB signaling pathway. Hepatobil Pancreat Dis Int 20(6):551–560. https://doi.org/10.1016/j.hbpd.2021.04.001
Giakoustidis DE, Iliadis S, Tsantilas D et al (2003) Blockade of Kupffer cells by gadolinium chloride reduces lipid peroxidation and protects liver from ischemia/reperfusion injury. Hepatogastroenterology 50(53):1587–1592
Giakoustidis AE, Giakoustidis DE, Iliadis S et al (2006) Attenuation of intestinal ischemia/reperfusion induced liver and lung injury by intraperitoneal administration of (−)-epigallocatechin-3-gallate. Free Radic Res 40(1):103–110. https://doi.org/10.1080/10715760500133479
Giakoustidis DE, Giakoustidis AE, Iliadis S et al (2010) Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3-gallate via down-regulation of NF-κB and c-Jun expression. J Surg Res 159(2):720–728. https://doi.org/10.1016/j.jss.2008.08.038
Güçlü A, Koçak C, Koçak FE et al (2017) MicroRNA-125b as a new potential biomarker on diagnosis of renal ischemia–reperfusion injury. J Surg Res 207:241–248. https://doi.org/10.1016/j.jss.2016.08.067
Hatano E (2007) Tumor necrosis factor signaling in hepatocyte apoptosis. J Gastroenterol Hepatol 22:S43–S44. https://doi.org/10.1111/j.1440-1746.2006.04645.x
Hevia H, Varela-Rey M, Corrales FJ et al (2004) 5′-Methylthioadenosine modulates the inflammatory response to endotoxin in mice and in rat hepatocytes. Hepatology 39(4):1088–1098. https://doi.org/10.1002/hep.20154
Hikim APS, Lue YH, Wang C et al (2000) Posttesticular antifertility action of triptolide in the male rat: evidence for severe impairment of cauda epididymal sperm ultrastructure. J Androl 21(3):431–437
Hinnebusch BF, Meng S, Wu JT et al (2002) The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J Nutr 132(5):1012–1017. https://doi.org/10.1093/jn/132.5.1012
Huang Z, Zheng D, Pu J et al (2019) MicroRNA-125b protects liver from ischemia/reperfusion injury via inhibiting TRAF6 and NF-κB pathway. Biosci Biotechnol Biochem 83(5):829–835. https://doi.org/10.1080/09168451.2019.1569495
Husted TL, Lentsch AB (2006) The role of cytokines in pharmacological modulation of hepatic ischemia/reperfusion injury. Curr Pharm Des 12(23):2867–2873. https://doi.org/10.2174/138161206777947597
Jaeschke H (1991) Reactive oxygen and ischemia/reperfusion injury of the liver. Chemico-Bio Int 79:115–136. https://doi.org/10.1016/0009-2797(91)90077-K
Jelkmann W (2013) Physiology and pharmacology of erythropoietin. Transfus Med Hemother 40(5):302–309. https://doi.org/10.1159/00035619310.1016/j.biopha.2021.112374
Jiao SF, Sun K, Chen XJ et al (2014) Inhibition of tumor necrosis factor alpha reduces the outgrowth of hepatic micrometastasis of colorectal tumors in a mouse model of liver ischemia-reperfusion injury. J Biomed Sci 21:1. https://doi.org/10.1186/1423-0127-21-1
Jiao Z, Ma Y, Liu X et al (2019) Adipose-derived stem cell transplantation attenuates inflammation and promotes liver regeneration after ischemia-reperfusion and hemihepatectomy in swine. Stem Cells Int 2019. https://doi.org/10.1155/2019/2489584
Jin X, Wang J, Xia ZM et al (2016) Anti-inflammatory and anti-oxidative activities of paeonol and its metabolites through blocking MAPK/ERK/p38 signaling pathway. Inflammation 39:434–446. https://doi.org/10.1007/s10753-015-0265-3
Kakaei F, Fasihi M, Hashemzadeh S et al (2020) Effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in obstructive jaundice: a randomized controlled trial. Asian J Surg 43:322–329. https://doi.org/10.1016/j.asjsur.2019.05.009
Kalogeris T, Baines CP, Krenz M et al (2012) Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 298:229–317. https://doi.org/10.1016/B978-0-12-394309-5.00006-7
Kaltenmeier C et al (2022) Role of immuno-inflammatory signals in liver ischemia-reperfusion injury. Cells 11(14):2222. https://doi.org/10.3390/cells11142222
Kawakami S, Suzuki Yamashita SF, Hashida M (2006) Induction of apoptosis in A549 human lung cancer cells by all-trans retinoic acid incorporated in DOTAP/cholesterol liposomes. J Control Release 110(3):514–521. https://doi.org/10.1016/j.jconrel.2005.10.030
Ke B, Lipshutz GS, Kupiec-Weglinski JW (2006) Gene therapy in liver ischemia and reperfusion injury. Curr Pharm Des 12:2969–2975. https://doi.org/10.2174/138161206777947669
Khan AW, Fuller BJ, Shah SR et al (2005) A prospective randomized trial of N-acetyl cysteine administration during cold preservation of the donor liver for transplantation. Ann Hepatol 4:121–126
Kim JW, Kim JD, Yu SB et al (2013) Comparison of hepatic and renal function between inhalation anesthesia with sevoflurane and remifentanil and total intravenous anesthesia with propofol and remifentanil for thyroidectomy. Kor J Anesth 64(2):112–116. https://doi.org/10.4097/kjae.2013.64.2.112
Kimura Y, Yokoi K, Matsushita N et al (1997) Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells. J Pharm Pharmcol 49(8):816–822. https://doi.org/10.1111/j.2042-7158.1997.tb06119.x
Kincius M, Liang R, Nickkholgh A et al (2007) Taurine protects from liver injury after warm ischemia in rats: the role of Kupffer cells. Eur Surg Res 39(5):275–283. https://doi.org/10.1159/000102982
Klune JR, Tsung A (2010) A Molecular biology of liver ischemia/reperfusion injury: established mechanisms and recent advancements. Surg Clin N Am 90:665–677. https://doi.org/10.1016/j.suc.2010.04.003
Koh SH, Kim SH, Kwon H et al (2003) Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3. Brain Res Mol Brain Res 118(1–2):72–81. https://doi.org/10.1016/j.molbrainres.2003.07.003
Kondo H, Park SH, Watanabe K et al (2004) Polyphenol (−)-epigallocatechin gallate inhibits apoptosis induced by irradiation in human HaCaT keratinocytes. Biochem Biophys Res Commun 316(1):59–64. https://doi.org/10.1016/j.bbrc.2004.01.175
Konishi T, Lentsch AB (2017) Lentsch, hepatic ischemia/reperfusion: mechanisms of tissue injury, repair, and regeneration. Gene Expr 17(4):277–287. https://doi.org/10.3727/105221617X15042750874156
Kuboki S, Tomohisa O, Rebecca S et al (2007) Hepatocyte NF-κB activation is hepatoprotective during ischemia-reperfusion injury and is augmented by ischemic hypothermia. Am J Physiol Gastrointest Liver Physiol 292(1):G201–G207. https://doi.org/10.1152/ajpgi.00186.2006
Lawrence T (2009) The nuclear factor NF-κB pathway in inflammation. Cold Spring Harbor Perspect Biol 1:a 001651. https://doi.org/10.1101/cshperspect.a001651
Lee J, Kim YS, Lee JH et al (2016) Walnut phenolic extract and its bioactive compounds suppress colon cancer cell growth by regulating colon cancer stemness. Nutrients 8(7):439. https://doi.org/10.3390/nu8070439
Leung DW, Cachianes G, Kuang WJ et al (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935):1306–1309. https://doi.org/10.1126/science.2479986
Li J, Ke W, Zhou Q et al (2014) Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway. J Cell Mol Med 18:1863–1873. https://doi.org/10.1111/jcmm.12320
Li H, Sun JJ, Chen GY et al (2016) Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, caspases and NF-κB signaling pathway in mice. Biomed Pharmacother 82:237–246. https://doi.org/10.1016/j.biopha.2016.04.064
Li X, Wang L, Yang X, Huang C (2020) Metformin attenuates ischemia-reperfusion injury of fatty liver in rats through inhibition of the TLR4/NF-κB axis. Balkan Med J 37(4):196
Liang Y, Shen T, Ming Q et al (2018) Alpinetin ameliorates inflammatory response in LPS-induced endometritis in mice. Int Immunopharmacol 62:309–312
Liao X, Zhou S, Zong J et al (2019) Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p. Exp Ther Med 17(4):2632–2640. https://doi.org/10.3892/etm.2019.7272
Lin J, Huang H, Yang S et al (2020) Protective effects of ischemic preconditioning protocols on ischemia-reperfusion injury in rat liver. J Invest Surg 33:876–883. https://doi.org/10.1080/08941939.2018.1556753
Liu PT, Krutzik SR, Kim J et al (2005) Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function. J Immunol 174(5):2467–2470. https://doi.org/10.4049/jimmunol.174.5.2467
Liu B, Jian Z, Li Q et al (2012) Baicalein protects human melanocytes from H2O2-induced apoptosis via inhibiting mitochondria-dependent caspase activation and the p38 MAPK pathway. Free Radic Biol Med 53(2):183–193. https://doi.org/10.1016/j.freeradbiomed.2012.04.015
Liu QS, Cheng ZW, Xiong JG et al (2015a) Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia/reperfusion-injured rats via suppression of the TLR2/NF-κB pathway. Transp Proc 47(2):283–289. https://doi.org/10.1016/j.transproceed.2014.10.045
Liu A, Huang L, Fan H et al (2015b) Baicalein pretreatment protects against liver ischemia/reperfusion injury via inhibition of NF-κB pathway in mice. Int Immunopharmacol Int Immunopharmacol 24(1):72–79. https://doi.org/10.1016/j.intimp.2014.11.014
Lu L, Zhou H, Ni M et al (2016) Innate immune regulations and liver ischemia reperfusion injury. Transplantation 100:2601. https://doi.org/10.1097/TP.0000000000001411
Ma H, Wang X, Ha T et al (2016) MicroRNA-125b prevents cardiac dysfunction in polymicrobial sepsis by targeting TRAF6-mediated nuclear factor κB activation and p53-mediated apoptotic signaling. J Infect Dis 214(11):1773–1783. https://doi.org/10.1093/infdis/jiw449
Ma G et al (2020) Ribonuclease alleviates hepatic ischemia-reperfusion injury by suppressing excessive cytokine release and TLR3-mediated apoptosis in mice. Cytokine 133:155178. https://doi.org/10.1016/j.cyto.2020.155178
Mahmoud MF, El Shazly SM, Barakat W (2012) Inhibition of TNF-α protects against hepatic ischemia–reperfusion injury in rats via NF-κB dependent pathway. Naunyn-Schmiedeberg’s Arch Pharmacol 385(5):465–471. https://doi.org/10.1007/s00210-012-0729-z
Mahmoud HM, Elsayed Abouzed DE, Abo-Youssef AM et al (2023) Zafirlukast protects against hepatic ischemia–reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways. Int Immunopharmacol 122:110498. https://doi.org/10.1016/j.intimp.2023.110498
Maini R, St Calir EW, Breedveld F et al (1999) (1999) Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet 354(9194):1932–1939. https://doi.org/10.1016/s0140-6736(99)05246-0
Masior Ł, Grąt M (2021) Methods of attenuating ischemia-reperfusion injury in liver transplantation for hepatocellular carcinoma. Int J Mol Sci 22:8229. https://doi.org/10.3390/ijms22158229
Mehta K, McQueen T, Tucker S et al (1994) Inhibition by all-trans-retinoic acid of tumor necrosis factor and nitric oxide production by peritoneal macrophages. J Leukoc Biol 55(3):336–342. https://doi.org/10.1002/jlb.55.3.336
Meijer K, de Vos P, Priebe MG (2010) Butyrate and other short-chain fatty acids as modulators of immunity: what relevance for health? Curr Opin Clin Nutr Metab Care 13(6):715–721. https://doi.org/10.1097/mco.0b013e32833eebe5
Mergental H, Perera M, Laing R et al (2016) Transplantation of declined liver allografts following normothermic ex-situ evaluation. Am J Transplant 16(11):3235–3245. https://doi.org/10.1111/ajt.13875
Morsy MA, Ibrahim YF, Abdel Hafez SMN (2022) Paeonol attenuates hepatic ischemia/reperfusion injury by modulating the Nrf2/HO-1 and TLR4/MYD88/NF-κB signaling pathways. Antioxidants 11(9):1687. https://doi.org/10.3390/antiox11091687
Muraoka KI, Shimizu K, Sun X et al (1997) Hypoxia, but not reoxygenation, induces interleukin 6 gene expression through NF-kB activation. Transplantation 63(3):466–470
Nastos C, Kalimeris K, Papoutsidakis N et al (2014) Global consequences of liver ischemia/reperfusion injury. Oxid Med Cell Longev. https://doi.org/10.1155/2014/906965
Pan Y, Yu S, Wang J et al (2021a) N-acetyl-L-tryptophan attenuates hepatic ischemia-reperfusion injury via regulating TLR4/NLRP3 signaling pathway in rats. Peer J 9:e11909. https://doi.org/10.7717/peerj.11909
Pan Y et al (2021b) N-acetyl-L-tryptophan attenuates hepatic ischemia-reperfusion injury via regulating TLR4/NLRP3 signaling pathway in rats. PeerJ 9:e11909
Pantazi E et al (2016) Advances in treatment strategies for ischemia reperfusion injury. Expert Opin Pharmacother 17(2):169–179. https://doi.org/10.1517/14656566.2016.1115015
Papadopoulos D, Siempis T, Theodorakou E, Tsoulfas G (2013) Hepatic ischemia and reperfusion injury and trauma: current concepts. Arch Trauma Res 2:63–70. https://doi.org/10.5812/atr.12501
Pirklbauer M (2021) Anti-inflammatory potential of empagliflozin. Inflammopharmacology 29(2):573–576. https://doi.org/10.1007/s10787-021-00797-9
Qiao YL, Qian JM, Wang FR et al (2014) Butyrate protects liver against ischemia reperfusion injury by inhibiting nuclear factor kappa B activation in Kupffer cells. J Surg Res 187(2):653–659. https://doi.org/10.1016/j.jss.2013.08.028
Qiu D, Kao PN (2003) Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. Drugs R D 4:1–18. https://doi.org/10.2165/00126839-200304010-00001
Ramachandran S, Liaw JM, Jia J et al (2012) Ischemia–reperfusion injury in rat steatotic liver is dependent on NFκB P65 activation. Transp Immunol 26(4):201–206. https://doi.org/10.1016/j.trim.2012.01.001
Rao J, Qian X, Wang P et al (2013) All-trans retinoic acid preconditioning protects against liver ischemia/reperfusion injury by inhibiting the nuclear factor kappa B signaling pathway. J Surg Res 180(2):e99–e106. https://doi.org/10.1016/j.jss.2012.04.008
Ravikumar R, Jassem W, Mergental H et al (2016) Liver transplantation after ex vivo normothermic machine preservation: a phase 1 (first-in-man) clinical trial. Am J Transplant 16(6):1779–1787. https://doi.org/10.1111/ajt.13708
Rodriguez-Reynoso S, Leal C, Portilla E et al (2001) Effect of exogenous melatonin on hepatic energetic status during ischemia/reperfusion: possible role of tumor necrosis factor-α and nitric oxide. J Surg Res 100(2):141–149. https://doi.org/10.1006/jsre.2001.6185
Saleh H, El-Shorbagy HM (2020) Chitosan protects liver against ischemia-reperfusion injury via regulating Bcl-2/Bax, TNF-α and TGF-β expression. Int J Biol Macro 164:1565–1574. https://doi.org/10.1016/j.ijbiomac.2020.07.212
Santiago F, Bueno P, Olmedo C et al (2008) Effect of N-acetylcysteine administration on intraoperative plasma levels of interleukin-4 and interleukin-10 in liver transplant recipients, in Transplantation Proceedings pp 2978–2980. Elsevier. https://doi.org/10.1016/j.transproceed.2008.08.103
Schwabe RF, Brenner DA (2006) Mechanisms of liver injury. I. TNF-α-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol-Gastrointest Liver Physiol 290:G583–G589. https://doi.org/10.1152/ajpgi.00422.2005
ShenY C, Chiou WF, Chou YC et al (2003) Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. Eur J Pharmacol 465(1):171–181. https://doi.org/10.1016/s0014-2999(03)01378-5
Sherif IO, Al-Shaalan NH (2018) Vildagliptin attenuates hepatic ischemia/reperfusion injury via the TLR4/NF-κB signaling pathway. Oxid Med Cell Longev. https://doi.org/10.1155/2018/3509091
Shiratori Y, Kiriyama H, Fukushi Y et al (1994) Modulation of ischemia-reperfusion-induced hepatic injury by Kupffer cells. Dig Dis Sci 39:1265–1272. https://doi.org/10.1007/bf02093792
Singh CK, George J, Ahmad N (2013) Resveratrol-based combinatorial strategies for cancer management. Ann N Y Acad Sci 1290(1):113–121. https://doi.org/10.1111/nyas.12160
Soares RO, Losada DM, Jordani MC et al (2019) Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci 20:5034. https://doi.org/10.3390/ijms20205034
Soleas GJ, Diamandis EP, Goldberg DM (1997) Wine as a biological fluid: history, production, and role in disease prevention. J Clin Lab Anal 11(5):287–313. https://doi.org/10.1002/(sici)1098-2825(1997)11:5%3c287::aid-jcla6%3e3.0.co;2-4
Sosa RA et al (2016) Early cytokine signatures of ischemia/reperfusion injury in human orthotopic liver transplantation. JCI Insight 1(20). https://doi.org/10.1172/jci.insight.89679
Sun K, Chen Y, Liang SY et al (2012) Effect of taurine on IRAK4 and NF-kappa B in Kupffer cells from rat liver grafts after ischemia-reperfusion injury. Am J Surg 204(3):389–395. https://doi.org/10.1016/j.amjsurg.2011.10.020
Tamagawa K, Horiuchi T, Uchinami M et al (2008) Hepatic ischemia-reperfusion increases vascular endothelial growth factor and cancer growth in rats. J Surg Res 148(2):158–163. https://doi.org/10.1016/j.jss.2007.12.787
Tan Z, Jiang R, Wang X et al (2013) RORγt+IL-17+ neutrophils play a critical role in hepatic ischemia–reperfusion injury. J Mol Cel Biol 5:143–146. https://doi.org/10.1093/jmcb/mjs065
Tang Y, Zhang W, Zhang Y et al (2014) 5′-Methylthioadenosine attenuates ischemia reperfusion injury after liver transplantation in rats. Inflammation 37(5):1366–1373. https://doi.org/10.1007/s10753-014-9861-x
Tao X, Lipsky PE (2000) The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin N Am 26(1):29–50. https://doi.org/10.1016/s0889-857x(05)70118-6
Tili E, Michaille JJ, Cimino A et al (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179(8):5082–5089. https://doi.org/10.4049/jimmunol.179.8.5082
Tiriveedhi V, Upadhya GA, Busch RA et al (2014) Protective role of bortezomib in steatotic liver ischemia/reperfusion injury through abrogation of MMP activation and YKL-40 expression. Transpl Immunol 30(2–3):93–98. https://doi.org/10.1016/j.trim.2013.12.003
Tsurui Y, Sho M, Kuzumoto Y et al (2005) Dual role of vascular endothelial growth factor in hepatic ischemia-reperfusion injury. Transplantation 79(9):1110-1115. https://doi.org/10.1097/01.tp.0000161627.84481.5e
Van Rijt WG, Nieuwenhuijs-Moeke GJ, Van Goor H et al (2013) Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury. J Transl Med 11(1):286. https://doi.org/10.1186/1479-5876-11-286
Wang L, Li N, Lin D et al (2017) Curcumin protects against hepatic ischemia/reperfusion induced injury through inhibiting TLR4/NF-κB pathway. Oncotarget 8(39):65414. https://doi.org/10.18632/oncotarget.18676
Wiseman SA, Balentine DA, Frei B (1997) Antioxidants in tea. Crit Rev Food Sci Nutr 37(8):705–718. https://doi.org/10.1080/10408399709527798
Wolf AM, Wolf D, Rumpold H et al (2004) Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun 323:630–635. https://doi.org/10.1016/j.bbrc.2004.08.145
Wu C, Wang P, Rao J et al (2011) Triptolide alleviates hepatic ischemia/reperfusion injury by attenuating oxidative stress and inhibiting NF-κB activity in mice. J Surg Res 166(2):e205–e213. https://doi.org/10.1016/j.jss.2010.10.005
Xiao Q, Ye QF, Wang W et al (2017) Mild hypothermia pretreatment protects hepatocytes against ischemia reperfusion injury via down-regulating miR-122 and IGF-1R/AKT pathway. Cryobiology 75:100–105. https://doi.org/10.1016/j.cryobiol.2017.01.005
Xiao Q, Liu Y, Zhang X et al (2022) Mild hypothermia ameliorates hepatic ischemia reperfusion injury by inducing RBM3 expression. Apoptosis 27:899–912
Xu H, Berendsen T, Kim K et al (2012) Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia. J Surg Res 173(2):e83–e88. https://doi.org/10.1016/j.jss.2011.09.057
Ye Y, Perez-Polo JR, Aguilar D et al (2011) The potential effects of anti-diabetic medications on myocardial ischemia–reperfusion injury. Basic Res Cariol 106(6):925–952. https://doi.org/10.1007/s00395-011-0216-6
Yu HB, Zhang H, Zhang FX et al (2010) Resveratrol inhibits VEGF expression of human hepatocellular carcinoma cells through a NF-kappa B-mediated mechanism. Hepatogastroenterology 57(102–103):1241–1246
Yu Q et al (2019a) Protective effects of levo-tetrahydropalmatine on hepatic ischemia/reperfusion injury are mediated by inhibition of the ERK/NF-κB pathway. Int Immunopharmacol 70:435–445. https://doi.org/10.1016/j.intimp.2019.02.024
Zhang DY, Wu J, Ye F et al (2003) Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis. Cancer Res 63(14):4037–4043
Zhang JX, Wu HS, Wang H et al (2005) Protection against hepatic ischemia/reperfusion injury via downregulation of Toll-like receptor 2 expression by inhibition of Kupffer cell function. World J Gastroenterol 11(28):4423–6. https://doi.org/10.3748/wjg.v11.i28.4423
Zhang M, Li W, Yu L et al (2014) The suppressive effect of resveratrol on HIF-1α and VEGF expression after warm ischemia and reperfusion in rat liver. PLoS ONE 9(10):e109589. https://doi.org/10.1371/journal.pone.0109589
Zhang S, Feng Z, Gao W et al (2020) Aucubin attenuates liver ischemia-reperfusion injury by inhibiting the HMGB1/TLR-4/NF-κB signaling pathway, oxidative stress, and apoptosis. Front Pharm 11:1431. https://doi.org/10.3389/fphar.2020.544124
Zhou Y, Ding YL, Zhang JL et al (2018) Alpinetin improved high fat diet-induced non-alcoholic fatty liver disease (NAFLD) through improving oxidative stress, inflammatory response and lipid metabolism. Biomed Pharmacother 97:1397–1408. https://doi.org/10.1016/j.biopha.2017.10.035
Zhou X, Cai J, Liu W et al (2019) Cysteinyl leukotriene receptor type 1 (CysLT1R) antagonist zafirlukast protects against TNF-α-induced endothelial inflammation. Biomed Pharmacother 111:452–459. https://doi.org/10.1016/j.biopha.2018.12.064
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The authors would like to thank the Deanship of Scientific Research at Shaqra University for supporting this work.
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Moustafa O. Aboelez, visualization, methodology, and writing—original draft; Hend A. A. Ezelarab, formal analysis, writing (original draft), and conceptualization; Ghallab Alotaibi, investigation, resources, funding, and supervision; Deiaa E. Elsayed Abouzed, conceptualization, supervision, and writing (original draft). The authors confirm that no paper mill and artificial intelligence was used.
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Aboelez, M.O., Ezelarab, H.A.A., Alotaibi, G. et al. Inflammatory setting, therapeutic strategies targeting some pro-inflammatory cytokines and pathways in mitigating ischemia/reperfusion-induced hepatic injury: a comprehensive review. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03074-y
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DOI: https://doi.org/10.1007/s00210-024-03074-y