{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:23:25Z","timestamp":1785425005449,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1D1A1B03036295"],"award-info":[{"award-number":["2017R1D1A1B03036295"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2017R1D1A1B03036295"],"award-info":[{"award-number":["2017R1D1A1B03036295"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["K2327461"],"award-info":[{"award-number":["K2327461"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]},{"award":["K2327461"],"award-info":[{"award-number":["K2327461"]}],"id":[{"id":"https:\/\/ror.org\/047dqcg40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation in which excessive cell death and the release of damage-associated molecular patterns (DAMPs) such as high-mobility group box 1 (HMGB1) amplify mucosal injury. Although necrosis\u2014particularly regulated forms including necroptosis and ferroptosis\u2014has emerged as a contributor to IBD pathogenesis, the therapeutic potential of targeting necrotic cell death remains incompletely explored. We investigated whether MIT-001 (previously known as NecroX-7), a mitochondria-targeted reactive oxygen species (ROS) scavenger with anti-necrotic activity, ameliorates intestinal inflammation in an acute dextran sulfate sodium (DSS)-induced colitis model. In vitro, MIT-001 reduced hydrogen peroxide-induced necrotic cell death in IEC-18 intestinal epithelial cells and was associated with a qualitative reduction in the 55-kDa cleaved poly(ADP-ribose) polymerase-1 (PARP-1) fragment (a marker of necrosis), with no apparent change in the apoptosis-related 89-kDa fragment. In vivo, oral administration of MIT-001 to C57BL\/6 mice with DSS-induced colitis was associated with preservation of colon length, reduced histological injury, and a marked decrease in HMGB1-positive cells in colonic tissue. Among pro-inflammatory cytokines, IL-1\u03b2 expression was significantly reduced, while IL-12, monocyte chemoattractant protein-1 (MCP-1), and TNF-\u03b1 showed non-significant downward trends. These findings indicate that MIT-001 ameliorates DSS-induced colitis in association with reduced HMGB1 and IL-1\u03b2 expression, supporting further investigation of mitochondria-targeted anti-necrotic strategies as a potential adjunctive approach in IBD.<\/jats:p>","DOI":"10.3390\/ijms27136051","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MIT-001, a Mitochondria-Targeted ROS Scavenger, Ameliorates DSS-Induced Colitis and Is Associated with Reduced HMGB1 and IL-1\u03b2 Expression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6767-426X","authenticated-orcid":false,"given":"Dongwoo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Ha","family":"Kim","sequence":"additional","affiliation":[{"name":"Mitoimmune Therapeutics Inc., Seoul 05836, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-9672","authenticated-orcid":false,"given":"Jung Wan","family":"Choe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-7715","authenticated-orcid":false,"given":"Seung Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5632-7091","authenticated-orcid":false,"given":"Jong Jin","family":"Hyun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Woo","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6566-1382","authenticated-orcid":false,"given":"Young Kul","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-2754","authenticated-orcid":false,"given":"Hyung Joon","family":"Yim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1202-075X","authenticated-orcid":false,"given":"Ja Seol","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan 15355, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1097\/01.MIB.0000195385.19268.68","article-title":"Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities","volume":"12","author":"Hanauer","year":"2006","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1053\/j.gastro.2025.08.039","article-title":"AGA clinical practice update on inpatient management of adults with inflammatory bowel disease: Expert review","volume":"170","author":"Hashash","year":"2026","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"s1","DOI":"10.1136\/gutjnl-2019-318484","article-title":"British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults","volume":"68","author":"Lamb","year":"2019","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/ibd\/izae163","article-title":"Comparative efficacy of biologics and small molecule therapies in improving patient-reported outcomes in ulcerative colitis: Systematic review and network meta-analysis","volume":"31","author":"Shehab","year":"2025","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S2468-1253(21)00312-5","article-title":"Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn\u2019s disease: A systematic review and network meta-analysis","volume":"6","author":"Singh","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7719","DOI":"10.1038\/sj.onc.1203249","article-title":"More than one way to die: Apoptosis, necrosis and reactive oxygen damage","volume":"18","author":"Fiers","year":"1999","journal-title":"Oncogene"},{"key":"ref_7","first-page":"165","article-title":"Cell death: Apoptosis versus necrosis (review)","volume":"21","author":"Kanduc","year":"2002","journal-title":"Int. J. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1136\/gutjnl-2011-301364","article-title":"Apoptosis, necrosis and necroptosis: Cell death regulation in the intestinal epithelium","volume":"62","author":"Neumann","year":"2013","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature10400","article-title":"Caspase-8 regulates TNF-\u03b1-induced epithelial necroptosis and terminal ileitis","volume":"477","author":"Martini","year":"2011","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature10273","article-title":"FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation","volume":"477","author":"Welz","year":"2011","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/ajg.2013.403","article-title":"Necroptosis is active in children with inflammatory bowel disease and contributes to heighten intestinal inflammation","volume":"109","author":"Pierdomenico","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Patankar, J.V., Bubeck, M., Acera, M.G., and Becker, C. (2023). Breaking bad: Necroptosis in the pathogenesis of gastrointestinal diseases. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1203903"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhou, P., Zhang, S., Wang, M., and Zhou, J. (2023). The induction mechanism of ferroptosis, necroptosis, and pyroptosis in inflammatory bowel disease, colorectal cancer, and intestinal injury. Biomolecules, 13.","DOI":"10.3390\/biom13050820"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41419-021-03559-1","article-title":"The emerging role of ferroptosis in intestinal disease","volume":"12","author":"Xu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.imlet.2020.06.005","article-title":"Ferroptosis mediated DSS-induced ulcerative colitis associated with Nrf2\/HO-1 signaling pathway","volume":"225","author":"Chen","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Xie, H., Cao, C., Shu, D., Liu, T., and Zhang, T. (2024). The important role of ferroptosis in inflammatory bowel disease. Front. Med., 11.","DOI":"10.3389\/fmed.2024.1449037"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1007\/s12272-010-1114-4","article-title":"NecroX as a novel class of mitochondrial reactive oxygen species and ONOO\u2212 scavenger","volume":"33","author":"Kim","year":"2010","journal-title":"Arch. Pharm. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1093\/cvr\/cvs122","article-title":"NecroX-5 prevents hypoxia\/reoxygenation injury by inhibiting the mitochondrial calcium uniporter","volume":"94","author":"Thu","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1016\/j.transproceed.2010.08.050","article-title":"Effect of necrosis modulator NecroX-7 on hepatic ischemia-reperfusion injury in beagle dogs","volume":"42","author":"Choi","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11712","DOI":"10.1021\/acs.jmedchem.4c00211","article-title":"Discovery of new phenyltetrazolium derivatives as ferroptosis inhibitors for treating ischemic stroke: An example development from free radical scavengers","volume":"67","author":"Lu","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15.25.1","DOI":"10.1002\/0471142735.im1525s104","article-title":"Dextran sulfate sodium (DSS)-induced colitis in mice","volume":"104","author":"Chassaing","year":"2014","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1136\/gut.2009.197822","article-title":"Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome","volume":"59","author":"Bauer","year":"2010","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1159\/000007822","article-title":"Characterisation of acute murine dextran sodium sulphate colitis: Cytokine profile and dose dependency","volume":"62","author":"Egger","year":"2000","journal-title":"Digestion"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"C817","DOI":"10.1152\/ajpcell.00139.2004","article-title":"Calcium, ATP, and ROS: A mitochondrial love-hate triangle","volume":"287","author":"Brookes","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tibs.2006.11.001","article-title":"Cell death by necrosis: Towards a molecular definition","volume":"32","author":"Golstein","year":"2007","journal-title":"Trends Biochem. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1104\/pp.010999","article-title":"Oxidative stress increased respiration and generation of reactive oxygen species, resulting in ATP depletion, opening of mitochondrial permeability transition, and programmed cell death","volume":"128","author":"Tiwari","year":"2002","journal-title":"Plant Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature00858","article-title":"Release of chromatin protein HMGB1 by necrotic cells triggers inflammation","volume":"418","author":"Scaffidi","year":"2002","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1084\/jem.192.4.565","article-title":"High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes","volume":"192","author":"Andersson","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nri1594","article-title":"High-mobility group box 1 protein (HMGB1): Nuclear weapon in the immune arsenal","volume":"5","author":"Lotze","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1080\/08916930701356978","article-title":"HMGB1: A signal of necrosis","volume":"40","author":"Raucci","year":"2007","journal-title":"Autoimmunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R71","DOI":"10.1186\/ar3332","article-title":"High mobility group box 1 (HMGB1) and anti-HMGB1 antibodies and their relation to disease characteristics in systemic lupus erythematosus","volume":"13","author":"Abdulahad","year":"2011","journal-title":"Arthritis Res. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1097\/01.CCM.0000155991.88802.4D","article-title":"Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock","volume":"33","author":"Rouhiainen","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/hep.25982","article-title":"High-mobility group box 1 (HMGB1)-Toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: Interaction of \u03b3\u03b4 T cells with macrophages","volume":"57","author":"Wang","year":"2013","journal-title":"Hepatology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1038\/ajg.2011.231","article-title":"Fecal HMGB1 is a novel marker of intestinal mucosal inflammation in pediatric inflammatory bowel disease","volume":"106","author":"Vitali","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_35","first-page":"23","article-title":"Roles of high-mobility group box 1 in murine experimental colitis","volume":"2","author":"Yamasaki","year":"2009","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e135","DOI":"10.1038\/ctg.2015.63","article-title":"Loss of response to anti-TNFs: Definition, epidemiology, and management","volume":"7","author":"Roda","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dashdorj, A., Jyothi, K.R., Lim, S., Jo, A., Nguyen, M.N., Ha, J., Yoon, K.S., Kim, H.J., Park, J.H., and Murphy, M.P. (2013). Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines. BMC Med., 11.","DOI":"10.1186\/1741-7015-11-178"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Fedorov, A.V., Chelombitko, M.A., Chernyavskij, D.A., Galkin, I.I., Pletjushkina, O.Y., Vasilieva, T.V., Zinovkin, R.A., and Chernyak, B.V. (2022). Mitochondria-targeted antioxidant SkQ1 prevents the development of experimental colitis in mice and impairment of the barrier function of the intestinal epithelium. Cells, 11.","DOI":"10.3390\/cells11213441"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1016\/j.ajpath.2014.05.019","article-title":"Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis","volume":"184","author":"Wang","year":"2014","journal-title":"Am. J. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/sj.cdd.4400851","article-title":"Characterization of the necrotic cleavage of poly(ADP-ribose) polymerase (PARP-1): Implication of lysosomal proteases","volume":"8","author":"Gobeil","year":"2001","journal-title":"Cell Death Differ."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:06:17Z","timestamp":1783346777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":40,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27136051"],"URL":"https:\/\/doi.org\/10.3390\/ijms27136051","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]}}}