{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T19:34:29Z","timestamp":1768073669127,"version":"3.49.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"an unrestricted ESOT (European Society of Transplantation) Transplant Fellowship Grant","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"an unrestricted ESOT (European Society of Transplantation) Transplant Fellowship Grant","award":["KOOR-UZ Leuven"],"award-info":[{"award-number":["KOOR-UZ Leuven"]}]},{"name":"Flanders Research Foundation","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"Flanders Research Foundation","award":["KOOR-UZ Leuven"],"award-info":[{"award-number":["KOOR-UZ Leuven"]}]},{"name":"University Hospitals Leuven","award":["1830517N"],"award-info":[{"award-number":["1830517N"]}]},{"name":"University Hospitals Leuven","award":["KOOR-UZ Leuven"],"award-info":[{"award-number":["KOOR-UZ Leuven"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Intestinal ischemia reperfusion injury (IRI) is a harmful process that occurs during intestinal infarction and intestinal transplantation (ITx). It is characterized by severe inflammation which disrupts the mucosal barrier, causing bacterial translocation and sepsis. Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid) (TL) is a synthetic compound with powerful anti-inflammatory properties. Objective: To investigate the effect of pretreatment with TL in a validated rat model of intestinal IRI (60 min of ischemia). Methods: TL (650 mg\/kg) was administered by oral gavage 24 and 2 h before the onset of ischemia. Experiment 1 examined 7-day survival in 3 study groups (sham, vehicle+IRI and TL+IRI, n = 10\/group). In Experiment 2, the effects on the intestinal wall integrity and inflammation were studied after 60 min of reperfusion using 3 groups (sham, IRI and TL+IRI, n = 6\/group). The following end-points were studied: L-lactate, intestinal fatty acid-binding protein (I-FABP), histology, intestinal permeability, endotoxin translocation, pro- and anti-inflammatory cytokines and heme oxygenase-1 (HO-1) levels. Experiment 3 examined the role of HO-1 upregulation in TL pretreatment, by blocking its expression using Zinc protoporphyrin (ZnPP) at 20 mg\/kg vs. placebo (n = 6\/group). Results: Intestinal IRI resulted in severe damage of the intestinal wall and a 10% 7-day survival. These alterations led to endotoxin translocation and upregulation of pro-inflammatory cytokines. TL pretreatment improved survival up to 50%, significantly reduced inflammation and protected the intestinal barrier. The HO-1 inhibitor ZnPP, abolished the protective effect of TL. Conclusions: TL pretreatment improves survival by protecting the intestinal barrier function, decreasing inflammation and endotoxin translocation, through upregulation of HO-1.This rat study of severe intestinal ischemia reperfusion injury demonstrates a novel role for Tranilast as a potential therapy. Administration of Tranilast led to a marked reduction in mortality, inflammation and intestinal permeability and damage. The study proved that Tranilast functions through upregulation of heme oxygenase-1.<\/jats:p>","DOI":"10.3390\/jcm14093254","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:46:19Z","timestamp":1746618379000},"page":"3254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tranilast Reduces Intestinal Ischemia Reperfusion Injury in Rats Through the Upregulation of Heme-Oxygenase (HO)-1"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4921-466X","authenticated-orcid":false,"given":"Emilio","family":"Canovai","sequence":"first","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-171X","authenticated-orcid":false,"given":"Ricard","family":"Farr\u00e9","sequence":"additional","affiliation":[{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gert","family":"De Hertogh","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translational Cell and Tissue Research, Department of Imaging & Pathology, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2839-8896","authenticated-orcid":false,"given":"Antoine","family":"Dubois","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8728-0903","authenticated-orcid":false,"given":"Tim","family":"Vanuytsel","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Translation Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, 3000 Leuven, Belgium"},{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8147-8801","authenticated-orcid":false,"given":"Jacques","family":"Pirenne","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Microbiology, Immunology and Transplantation, KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4261-7100","authenticated-orcid":false,"given":"Laurens J.","family":"Ceulemans","sequence":"additional","affiliation":[{"name":"Leuven Intestinal Failure and Transplantation Center (LIFT), University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Thoracic Surgery, University Hospitals Leuven, 3000 Leuven, Belgium"},{"name":"Department of Chronic Diseases and Metabolism (CHROMETA), Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), KU Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1093\/ajcn\/75.5.789","article-title":"Protective nutrients and functional foods for the gastrointestinal tract","volume":"75","author":"Duggan","year":"2002","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1136\/gut.2005.085373","article-title":"Alterations in intestinal permeability","volume":"55","author":"Arrieta","year":"2006","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1023\/B:DDAS.0000042232.98927.91","article-title":"Ischemia\u2013Reperfusion Injury of the Intestine and Protective Strategies Against Injury","volume":"49","author":"Mallick","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1097\/01.sla.0000154269.52294.57","article-title":"Clinical implications for the management of acute thromboembolic occlusion of the superior mesenteric artery: Autopsy findings in 213 patients","volume":"241","author":"Acosta","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1053\/j.semvascsurg.2009.12.001","article-title":"Epidemiology of mesenteric vascular disease: Clinical implications","volume":"23","author":"Acosta","year":"2010","journal-title":"Semin. Vasc. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0002-9610(97)89619-5","article-title":"Nonocclusive mesenteric ischemia remains a diagnostic dilemma","volume":"171","author":"Howard","year":"1996","journal-title":"Am. J. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1111\/j.1365-2796.2006.01613.x","article-title":"Fatal nonocclusive mesenteric ischaemia: Population-based incidence and risk factors","volume":"259","author":"Acosta","year":"2006","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/nm.2507","article-title":"Ischemia and reperfusion--from mechanism to translation","volume":"17","author":"Eltzschig","year":"2011","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/bjs.4459","article-title":"Systematic review of survival after acute mesenteric ischaemia according to disease aetiology","volume":"91","author":"Schoots","year":"2004","journal-title":"Br. J. Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ejvs.2017.01.010","article-title":"Editor\u2019s Choice\u2014Management of the Diseases of Mesenteric Arteries and Veins","volume":"53","author":"Koelemay","year":"2017","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/j.jvs.2015.06.204","article-title":"Revascularization of acute mesenteric ischemia after creation of a dedicated multidisciplinary center","volume":"62","author":"Roussel","year":"2015","journal-title":"J. Vasc. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/j.1445-2197.1998.tb02099.x","article-title":"Ischaemia-reperfusion injury to the intestine","volume":"68","author":"Kong","year":"1998","journal-title":"Aust. N. Z. J. Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.18433\/J3JG7D","article-title":"Intestinal P-glycoprotein Expression is Multimodally Regulated by Intestinal Ischemia-Reperfusion","volume":"17","author":"Terada","year":"2014","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Andr\u00e9s Juan, C., Manuel P\u00e9rez de la Lastra, J., Plou, F.J., P\u00e9rez-Lebe\u00f1a, E., and Reinbothe, S. (2021). Molecular Sciences The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094642"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ulusoy Tangul, S., Onat, T., Aydo\u011fan Kirmizi, D., Doganyigit, Z., Kaymak, E., Oflamaz, A., \u015eenayli, A., and Somuncu, S. (2024). Effect of bromelain on ischemia-reperfusion injury in the torsion model created in polycystic and normal ovarian tissues. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1451592"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.urology.2014.07.022","article-title":"Beneficial effect of nifedipine on testicular torsion-detorsion injury in rats","volume":"84","year":"2014","journal-title":"Urology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/ajt.12979","article-title":"Intestinal Transplant Registry Report: Global Activity and Trends","volume":"15","author":"Grant","year":"2015","journal-title":"Am. J. Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.2353\/ajpath.2010.091069","article-title":"Human intestinal ischemia-reperfusion-induced inflammation characterized: Experiences from a new translational model","volume":"176","author":"Grootjans","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1097\/MOT.0b013e32835ef1eb","article-title":"New insights in intestinal ischemia\u2013reperfusion injury","volume":"18","author":"Lenaerts","year":"2013","journal-title":"Curr. Opin. Organ. Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.phrs.2014.10.009","article-title":"Tranilast: A review of its therapeutic applications","volume":"91","author":"Darakhshan","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1124\/pr.107.07104","article-title":"Pharmacological and clinical aspects of heme oxygenase","volume":"60","author":"Abraham","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.bbrc.2008.04.054","article-title":"Tranilast, an orally active anti-allergic drug, up-regulates the anti-inflammatory heme oxygenase-1 expression but down-regulates the pro-inflammatory cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW264.7 macrophages","volume":"371","author":"Pae","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/ndt\/gfq355","article-title":"Tranilast attenuates the up-regulation of thioredoxin-interacting protein and oxidative stress in an experimental model of diabetic nephropathy","volume":"26","author":"Tan","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1046\/j.1472-8206.2001.00007.x","article-title":"The effect of pentoxifylline on intestinal ischemia\/reperfusion injury","volume":"15","author":"Sener","year":"2001","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.smim.2011.07.005","article-title":"Type 1 regulatory T cells (Tr1) in autoimmunity","volume":"23","author":"Pot","year":"2011","journal-title":"Semin. Immunol."},{"key":"ref_26","first-page":"446","article-title":"Effects of Tranilast on renal structure and function in mice with ischemic reperfusion injury","volume":"32","author":"Wang","year":"2012","journal-title":"J. Shanghai Jiaotong Univ. (Med. Sci.)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1111\/cts.12606","article-title":"Tranilast Treatment Attenuates Cerebral Ischemia-Reperfusion Injury in Rats Through the Inhibition of Inflammatory Responses Mediated by NF-\u03baB and PPARs","volume":"12","author":"Zhuo","year":"2019","journal-title":"Clin. Transl. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ceulemans, L.J., Verbeke, L., Decuypere, J.-P., Farr\u00e9, R., De Hertogh, G., Lenaerts, K., Jochmans, I., Monbaliu, D., Nevens, F., and Tack, J. (2017). Farnesoid x receptor activation attenuates intestinal ischemia reperfusion injury in rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169331"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Clarysse, M., Accarie, A., Panisello-Rosell\u00f3, A., Farr\u00e9, R., Canovai, E., Monbaliu, D., De Hertogh, G., Vanuytsel, T., Pirenne, J., and Ceulemans, L.J. (2023). Intravenous Polyethylene Glycol Alleviates Intestinal Ischemia-Reperfusion Injury in a Rodent Model. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310775"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"P27","DOI":"10.1186\/1479-5876-9-S2-P27","article-title":"Tranilast, an analogue of tryptophan catabolites, induces allograft tolerance by CD161+ cells","volume":"9","author":"Li","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_31","first-page":"162","article-title":"Protective effect of ischemic postconditioning on lung ischemia-reperfusion injury in rats and the role of heme oxygenase-1","volume":"12","author":"Xia","year":"2009","journal-title":"Chin. J. Traumatol.\u2014Engl. Ed."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"G1151","DOI":"10.1152\/ajpgi.90649.2008","article-title":"A guide to Ussing chamber studies of mouse intestine","volume":"296","author":"Clarke","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Thomson, A., Smart, K., Somerville, M.S., Lauder, S.N., Appanna, G., Horwood, J., Raj, L.S., Srivastava, B., Durai, D., and Scurr, M.J. (2019). The Ussing chamber system for measuring intestinal permeability in health and disease. BMC Gastroenterol., 19.","DOI":"10.1186\/s12876-019-1002-4"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/SLA.0b013e318207a767","article-title":"Early Diagnosis of Intestinal Ischemia Using Urinary and Plasma Fatty Acid Binding Proteins","volume":"253","author":"Thuijls","year":"2011","journal-title":"Ann. Surg."},{"key":"ref_35","first-page":"574","article-title":"The sequence of development of intestinal tissue injury after strangulation ischemia and reperfusion","volume":"107","author":"Park","year":"1990","journal-title":"Surgery"},{"key":"ref_36","first-page":"193","article-title":"Abnormal barrier function in gastrointestinal disorders","volume":"239","author":"Vicario","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Motulsky, H.J., and Brown, R.E. (2006). Detecting outliers when fitting data with nonlinear regression\u2014A new method based on robust nonlinear regression and the false discovery rate. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-123"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1007\/s11605-015-2830-3","article-title":"Acute Mesenteric Ischemia Is a More Common Cause than Expected of Acute Abdomen in the Elderly","volume":"19","author":"Manninen","year":"2015","journal-title":"J. Gastrointest. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3164\/jcbn.17-137","article-title":"Microbiome and intestinal ischemia\/reperfusion injury","volume":"63","author":"Nadatani","year":"2018","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, G., Wang, S., and Fan, Z. (2022). Oxidative Stress in Intestinal Ischemia-Reperfusion. Front. Med., 8.","DOI":"10.3389\/fmed.2021.750731"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/0091-6749(76)90054-3","article-title":"Inhibition of hypersensitivity reactions by a new drug, N(3\u2032,4\u2032-dimethoxycinnamoyl) anthranilic acid (N-5\u2032)","volume":"57","author":"Koda","year":"1976","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/j.1432-2277.2004.00031.x","article-title":"Studying the immunosuppressive role of indoleamine 2,3-dioxygenase: Tryptophan metabolites suppress rat allogeneic T-cell responses in vitro and in vivo","volume":"18","author":"Bauer","year":"2005","journal-title":"Transpl. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1476-5381.1976.tb08614.x","article-title":"Pharmacological properties of N-(3\u2032,4\u2032-dimethoxycinnamoyl) anthranilic acid (N-5\u2032), a new anti-atopic agent","volume":"58","author":"Azuma","year":"1976","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1476-5381.2009.00561.x","article-title":"The anti-allergic compound tranilast attenuates inflammation and inhibits bone destruction in collagen-induced arthritis in mice","volume":"159","author":"Shiota","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1136\/gut.2006.115469","article-title":"Long-term prospective pilot study with tranilast for the prevention of stricture progression in patients with Crohn\u2019s disease","volume":"56","author":"Oshitani","year":"2007","journal-title":"Gut"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1046\/j.1523-1755.2003.00897.x","article-title":"Heme oxygenase-1 attenuates ischemia\/reperfusion-induced apoptosis and improves survival in rat renal allografts","volume":"63","author":"Wagner","year":"2003","journal-title":"Kidney Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"778","DOI":"10.2337\/diabetes.54.3.778","article-title":"Absence of heme oxygenase-1 exacerbates myocardial ischemia\/reperfusion injury in diabetic mice","volume":"54","author":"Liu","year":"2005","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/physrev.00011.2005","article-title":"Heme oxygenase-1\/carbon monoxide: From basic science to therapeutic applications","volume":"86","author":"Ryter","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/74680","article-title":"Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway","volume":"6","author":"Otterbein","year":"2000","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3884","DOI":"10.2174\/1381612823666170413122439","article-title":"Therapeutic Potential of Heme Oxygenase-1\/carbon Monoxide System Against Ischemia-Reperfusion Injury","volume":"23","author":"Cheng","year":"2017","journal-title":"Curr. Pharm. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1172\/JCI32730","article-title":"Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice","volume":"118","author":"Chung","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1089\/ars.2013.5368","article-title":"Carbon Monoxide Confers Protection in Sepsis by Enhancing Beclin 1-Dependent Autophagy and Phagocytosis","volume":"20","author":"Lee","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_53","first-page":"433","article-title":"Carbon monoxide increases macrophage bacterial clearance through Toll-like receptor (TLR)4 expression","volume":"51","author":"Otterbein","year":"2005","journal-title":"Cell. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1046\/j.1365-2249.1999.00851.x","article-title":"Rapid intestinal ischaemia-reperfusion injury is suppressed in genetically mast cell-deficient Ws\/Ws rats","volume":"116","author":"Andoh","year":"1999","journal-title":"Clin. Exp. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"H861","DOI":"10.1152\/ajpheart.00740.2001","article-title":"Stabilization of mast cells by heme oxygenase-1: An anti-inflammatory role","volume":"283","author":"Takamiya","year":"2002","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Jeong, S., Kang, C., Park, S., Ju, S., Yoo, J.-W., Yoon, I.-S., Yun, H., and Jung, Y. (2021). Eletrophilic chemistry of tranilast is involved in its anti-colitic activity via nrf2-ho-1 pathway activation. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111092"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jss.2004.01.010","article-title":"Heme oxygenase-1 induction by hemin protects against gut ischemia\/reperfusion injury","volume":"118","author":"Attuwaybi","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ijsu.2006.06.001","article-title":"Heme oxygenase-1 upregulation protects against intestinal ischemia\/reperfusion injury: A laboratory based study","volume":"5","author":"Wasserberg","year":"2007","journal-title":"Int. J. Surg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0021-9150(98)00308-6","article-title":"Tranilast inhibits the proliferation of human coronary smooth muscle cell through the activation of p21waf1","volume":"143","author":"Kusama","year":"1999","journal-title":"Atherosclerosis"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.ejps.2009.12.009","article-title":"Novel crystalline solid dispersion of tranilast with high photostability and improved oral bioavailability","volume":"39","author":"Kawabata","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.cgh.2012.10.027","article-title":"Effects of a Multimodal Management Strategy for Acute Mesenteric Ischemia on Survival and Intestinal Failure","volume":"11","author":"Corcos","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1097\/TP.0000000000000491","article-title":"Role of innate and acquired immune mechanisms in clinical intestinal transplant rejection","volume":"99","author":"Mathew","year":"2015","journal-title":"Transplantation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1111\/ajt.13815","article-title":"The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation","volume":"16","author":"Ceulemans","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/imm.12026","article-title":"Suppression of the allogeneic response by the anti-allergy drug N-(3,4-dimethoxycinnamonyl) anthranilic acid results from T-cell cycle arrest","volume":"138","author":"Zaher","year":"2013","journal-title":"Immunology"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Prud\u2019Homme, G.J., Glinka, Y., Toulina, A., Ace, O., Subramaniam, V., and Jothy, S. (2010). Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013831"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1016\/j.celrep.2017.10.114","article-title":"The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells","volume":"21","author":"Ye","year":"2017","journal-title":"Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/cbf.1805","article-title":"Novel action of 3,4-DAA ameliorating acute liver allograft injury","volume":"29","author":"Sun","year":"2011","journal-title":"Cell Biochem. Funct."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/S0041-1345(00)01238-0","article-title":"An Evaluation of Methods for Grading Histologic Injury Following Ischemia\/Reperfusion of the Small Bowel","volume":"32","author":"Quaedackers","year":"2000","journal-title":"Transplant. Proc."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:55Z","timestamp":1760030935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14093254"],"URL":"https:\/\/doi.org\/10.3390\/jcm14093254","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}