{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:30:48Z","timestamp":1782289848973,"version":"3.54.5"},"reference-count":90,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T00:00:00Z","timestamp":1713571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Defense Medical Research and Materiel Command, Radiation Health Effects Research Program, Joint Program Committee 7","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}]},{"name":"Defense Medical Research and Materiel Command, Radiation Health Effects Research Program, Joint Program Committee 7","award":["1 I80 VP000264-01"],"award-info":[{"award-number":["1 I80 VP000264-01"]}]},{"name":"Defense Medical Research and Materiel Command, Radiation Health Effects Research Program, Joint Program Committee 7","award":["MED-11233"],"award-info":[{"award-number":["MED-11233"]}]},{"name":"USU Startup Funding","award":["DM178018"],"award-info":[{"award-number":["DM178018"]}]},{"name":"USU Startup Funding","award":["1 I80 VP000264-01"],"award-info":[{"award-number":["1 I80 VP000264-01"]}]},{"name":"USU Startup Funding","award":["MED-11233"],"award-info":[{"award-number":["MED-11233"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in G\u00f6ttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a G\u00f6ttingen minipig H-ARS model to investigate captopril\u2019s effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42\u20130.48 Gy\/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg\/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21\/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.<\/jats:p>","DOI":"10.3390\/ijms25084535","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"4535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the G\u00f6ttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome"],"prefix":"10.3390","volume":"25","author":[{"given":"Timothy","family":"Horseman","sequence":"first","affiliation":[{"name":"Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Bradley","family":"Rittase","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John E.","family":"Slaven","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry T.","family":"Bradfield","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Frank","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Comparative Pathology Division, Department of Laboratory Animal Resources, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn C.","family":"Hays","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Ott","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison R.","family":"Huppmann","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine, Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Pathology Department, Research Services, Naval Medical Research Center, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1256-0158","authenticated-orcid":false,"given":"David M.","family":"Burmeister","sequence":"additional","affiliation":[{"name":"Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina M.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.rpor.2011.06.001","article-title":"Radiobiology of the acute radiation syndrome","volume":"16","author":"Garau","year":"2011","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_2","unstructured":"(2022, November 08). Acute Radiation Syndrome: A Fact Sheet for Clinicians, Available online: https:\/\/www.cdc.gov\/nceh\/radiation\/emergencies\/arsphysicianfactsheet.htm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"014004","DOI":"10.1088\/1361-6498\/ac4ac6","article-title":"The acute radiation syndrome-need for updated medical guidelines","volume":"42","author":"Stenke","year":"2022","journal-title":"J. Radiol. Prot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1089\/ars.2013.5635","article-title":"Hematopoietic stem cell injury induced by ionizing radiation","volume":"20","author":"Shao","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15931","DOI":"10.3390\/ijms140815931","article-title":"Mechanisms of radiation toxicity in transformed and non-transformed cells","volume":"14","author":"Panganiban","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1667\/RR14406.1","article-title":"A review of radiation-induced coagulopathy and new findings to support potential prevention strategies and treatments","volume":"186","author":"Kennedy","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/stem.5530130731","article-title":"Heterogeneity of radiation sensitivity of hemopoietic stem cell subsets","volume":"13","author":"Wagemaker","year":"1995","journal-title":"Stem Cells"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.exphem.2011.01.010","article-title":"Sublethal radiation injury uncovers a functional transition during erythroid maturation","volume":"39","author":"Peslak","year":"2011","journal-title":"Exp. Hematol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dorr, H., and Meineke, V. (2011). Acute radiation syndrome caused by accidental radiation exposure-therapeutic principles. BMC Med., 9.","DOI":"10.1186\/1741-7015-9-126"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/00004032-200305000-00001","article-title":"Dose response relationships for acute ionizing-radiation lethality","volume":"84","author":"Anno","year":"2003","journal-title":"Health Phys."},{"key":"ref_11","first-page":"13","article-title":"Radiation poisoning: Current concepts in the acute radiation syndrome","volume":"3","author":"McCann","year":"2006","journal-title":"Am. J. Clin. Med."},{"key":"ref_12","unstructured":"Armed Forces Radiobiology Research Institute (2013). Medical Management of Radiological Casualties, Armed Forces Radiobiology Research Institute. [4th ed.]."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1186\/s13287-021-02373-y","article-title":"The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice","volume":"12","author":"Bensemmane","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/HP.0b013e318266ee13","article-title":"Acute gastrointestinal syndrome in high-dose irradiated mice","volume":"103","author":"Booth","year":"2012","journal-title":"Health Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1559325820956783","DOI":"10.1177\/1559325820956783","article-title":"At what dose can total body and whole abdominal irradiation cause lethal intestinal injury among C57BL\/6J mice?","volume":"18","author":"Gu","year":"2020","journal-title":"Dose Response"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaay9097","DOI":"10.1126\/science.aay9097","article-title":"Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites","volume":"370","author":"Guo","year":"2020","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1667\/RR2481.1","article-title":"Hematopoietic radiation syndrome in the Gottingen minipig","volume":"176","author":"Moroni","year":"2011","journal-title":"Radiat. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3109\/09553002.2014.892226","article-title":"Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: Early hematological changes and systemic inflammatory response syndrome in minipig","volume":"90","author":"Moroni","year":"2014","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1667\/RADE-21-00141.1","article-title":"Investigating the role of inflammasome caspases 1 and 11 in the acute radiation syndrome","volume":"196","author":"Daniel","year":"2021","journal-title":"Radiat. Res."},{"key":"ref_20","first-page":"2586305","article-title":"Sitagliptin alleviates radiation-induced intestinal injury by activating NRF2-antioxidant axis, mitigating NLRP3 inflammasome activation, and reversing gut microbiota disorder","volume":"2022","author":"Huang","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2022.01.068","article-title":"Ferroptosis plays an important role in promoting ionizing radiation-induced intestinal injuries","volume":"595","author":"Wang","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/s41419-020-2298-2","article-title":"Ferroptosis: Past, present and future","volume":"11","author":"Li","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3109\/09553002.2015.1054526","article-title":"Combined immunomodulator and antimicrobial therapy eliminates polymicrobial sepsis and modulates cytokine production in combined injured mice","volume":"91","author":"Elliott","year":"2015","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/gutjnl-2011-300367","article-title":"Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2\/cyclo-oxygenase-2-dependent manner","volume":"61","author":"Ciorba","year":"2012","journal-title":"Gut"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1136\/gutjnl-2018-316226","article-title":"Lactobacillus rhamnosus GG protects the intestinal epithelium from radiation injury through release of lipoteichoic acid, macrophage activation and the migration of mesenchymal stem cells","volume":"68","author":"Riehl","year":"2019","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1080\/19490976.2019.1709387","article-title":"Gut commensal derived-valeric acid protects against radiation injuries","volume":"11","author":"Li","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1177\/0023677219834593","article-title":"The use of non-rodent model species in microbiota studies","volume":"53","author":"Ericsson","year":"2019","journal-title":"Lab. Anim."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-4939-9581-3_9","article-title":"Characterization of the rat gut microbiota via 16S rRNA amplicon library sequencing","volume":"2018","author":"Ericsson","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s00335-021-09866-4","article-title":"The microbiome and rodent models of immune mediated diseases","volume":"32","author":"Hansen","year":"2021","journal-title":"Mamm. Genome"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jare.2022.05.011","article-title":"Alien species invasion of deep-sea bacteria into mouse gut microbiota","volume":"45","author":"Chu","year":"2023","journal-title":"J. Adv. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1182\/blood-2003-11-3828","article-title":"Inhibition of angiotensin I-converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells","volume":"104","author":"Charrier","year":"2004","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.exphem.2010.01.004","article-title":"Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation","volume":"38","author":"Davis","year":"2010","journal-title":"Exp. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.exphem.2010.12.002","article-title":"Captopril modulates hypoxia-inducible factors and erythropoietin responses in a murine model of total body irradiation","volume":"39","author":"Mungunsukh","year":"2011","journal-title":"Exp. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/s41598-019-38651-2","article-title":"Delayed captopril administration mitigates hematopoietic injury in a murine model of total body irradiation","volume":"9","author":"McCart","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rittase, W.B., McCart, E.A., Muir, J.M., Bouten, R.M., Slaven, J.E., Mungunsukh, O., Bylicky, M.A., Wilkins, W.L., Lee, S.H., and Gudmundsson, K.O. (2021). Effects of captopril against radiation injuries in the G\u00f6ttingen minipig model of hematopoietic-acute radiation syndrome. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256208"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3109\/09553002.2012.676228","article-title":"Accelerated hematopoietic recovery with angiotensin-(1-7) after total body radiation","volume":"88","author":"Rodgers","year":"2012","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/bs.vh.2017.02.001","article-title":"Erythropoietin regulation by angiotensin II","volume":"105","author":"Kim","year":"2017","journal-title":"Vitam. Horm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ncpcardio0449","article-title":"The hematopoietic system: A new niche for the renin-angiotensin system","volume":"3","author":"Hubert","year":"2006","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/stem.3339","article-title":"Renin-angiotensin system is involved in embryonic emergence of hematopoietic stem\/progenitor cells","volume":"39","author":"Julien","year":"2021","journal-title":"Stem Cells"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.intimp.2012.12.029","article-title":"Enhanced hematopoietic protection from radiation by the combination of genistein and captopril","volume":"15","author":"Day","year":"2013","journal-title":"Int. Immunopharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1016\/j.celrep.2020.02.049","article-title":"Transferrin receptor is a specific ferroptosis marker","volume":"30","author":"Feng","year":"2020","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fphys.2019.00139","article-title":"Mechanisms of ferroptosis and relations with regulated cell death: A Review","volume":"10","author":"Lei","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Rittase, W.B., Slaven, J.E., Suzuki, Y.J., Muir, J.M., Lee, S.H., Rusnak, M., Brehm, G.V., Bradfield, D.T., Symes, A.J., and Day, R.M. (2022). Iron deposition and ferroptosis in the spleen in a murine model of acute radiation syndrome. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911029"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"F702","DOI":"10.1152\/ajprenal.00044.2017","article-title":"Heme oxygenase-1 mitigates ferroptosis in renal proximal tubule cells","volume":"314","author":"Adedoyin","year":"2018","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41422-019-0263-3","article-title":"The role of ferroptosis in ionizing radiation-induced cell death and tumor suppression","volume":"30","author":"Lei","year":"2020","journal-title":"Cell Res."},{"key":"ref_46","first-page":"143","article-title":"Lipid peroxidation-dependent cell death regulated by GPX4 and ferroptosis","volume":"403","author":"Imai","year":"2017","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115164","DOI":"10.18632\/oncotarget.23046","article-title":"Molecular crosstalk between ferroptosis and apoptosis: Emerging role of ER stress-induced p53-independent PUMA expression","volume":"8","author":"Hong","year":"2017","journal-title":"Oncotarget"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/gut.50.1.71","article-title":"Activation of caspases in intestinal villus epithelial cells of normal and nematode infected rats","volume":"50","author":"Hyoh","year":"2002","journal-title":"Gut"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/j.1365-2982.2006.00795.x","article-title":"Constitutive expression of cyclooxygenase-2 in the neuromuscular compartment of normal human colon","volume":"18","author":"Bernardini","year":"2006","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1667\/RR1742.1","article-title":"Influence of sublethal total-body irradiation on immune cell populations in the intestinal mucosa","volume":"173","author":"Garg","year":"2010","journal-title":"Radiat. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Cui, W., Hull, L., Zizzo, A., Wang, L., Lin, B., Zhai, M., and Xiao, M. (2022). Pharmacokinetic study of rhIL-18BP and its effect on radiation-induced cytokine changes in mouse serum and intestine. Toxics, 11.","DOI":"10.3390\/toxics11010035"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Wang, A., Ling, Z., Yang, Z., Kiela, P.R., Wang, T., Wang, C., Cao, L., Geng, F., Shen, M., and Ran, X. (2015). Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: A pilot study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126312"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s00441-020-03206-9","article-title":"The pig as a model for immunology research","volume":"380","author":"Pabst","year":"2020","journal-title":"Cell Tissue Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bone.2018.10.005","article-title":"Lowering iron levels protects against bone loss in focally irradiated and contralateral femurs through distinct mechanisms","volume":"120","author":"Zhang","year":"2019","journal-title":"Bone"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1080\/09553002.2020.1708993","article-title":"Ionizing radiation induces ferroptosis in granulocyte-macrophage hematopoietic progenitor cells of murine bone marrow","volume":"96","author":"Zhang","year":"2020","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.exphem.2020.03.004","article-title":"Deposition of iron in the bone marrow of a murine model of hematopoietic acute radiation syndrome","volume":"84","author":"Rittase","year":"2020","journal-title":"Exp. Hematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41392-022-01090-z","article-title":"ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage","volume":"7","author":"Ma","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1093\/jrr\/rraa142","article-title":"Captopril reduces lung inflammation and accelerated senescence in response to thoracic radiation in mice","volume":"62","author":"Mungunsukh","year":"2021","journal-title":"J. Radiat. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1093\/jrr\/rrv071","article-title":"Expression analysis of radiation-responsive genes in human hematopoietic stem\/progenitor cells","volume":"57","author":"Tsujiguchi","year":"2016","journal-title":"J. Radiat. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1038\/s41598-023-37981-6","article-title":"Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem\/progenitor cells using integrated bioinformatics methods","volume":"13","author":"Sato","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_61","first-page":"101","article-title":"Idiopathic pneumonia syndrome after bone marrow transplantation: The role of pre-transplant radiation conditioning and local cytokine dysregulation in promoting lung inflammation and fibrosis","volume":"82","author":"Shankar","year":"2001","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"24214","DOI":"10.1038\/s41598-021-03636-7","article-title":"Transcriptomic profiling and pathway analysis of cultured human lung microvascular endothelial cells following ionizing radiation exposure","volume":"11","author":"Bouten","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Pan, H., Jian, Y., Wang, F., Yu, S., Guo, J., Kan, J., and Guo, W. (2022). NLRP3 and gut microbiota homeostasis: Progress in research. Cells, 11.","DOI":"10.3390\/cells11233758"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"643283","DOI":"10.3389\/fphar.2021.643283","article-title":"Acute radiation syndrome and the microbiome: Impact and review","volume":"12","author":"Hollingsworth","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Cheema, A.K., Li, Y., Singh, J., Johnson, R., Girgis, M., Wise, S.Y., Fatanmi, O.O., Kaytor, M.D., and Singh, V.K. (2021). Microbiome study in irradiated mice treated with BIO 300, a promising radiation countermeasure. Anim. Microbiome, 3.","DOI":"10.1186\/s42523-021-00132-1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1667\/RR14975.1","article-title":"Specific members of the gut microbiota are reliable biomarkers of irradiation intensity and lethality in large animal models of human health","volume":"191","author":"Carbonero","year":"2019","journal-title":"Radiat. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00411-018-0759-0","article-title":"A comparative analysis of gut microbiota disturbances in the Gottingen minipig and rhesus macaque models of acute radiation syndrome following bioequivalent radiation exposures","volume":"57","author":"Carbonero","year":"2018","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kalkeri, R., Walters, K., Van Der Pol, W., McFarland, B.C., Fisher, N., Koide, F., Morrow, C.D., and Singh, V.K. (2021). Changes in the gut microbiome community of nonhuman primates following radiation injury. BMC Microbiol., 21.","DOI":"10.1186\/s12866-021-02146-w"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2263210","DOI":"10.1080\/19490976.2023.2263210","article-title":"The influence of microbiota on ferroptosis in intestinal diseases","volume":"15","author":"Yao","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Khan, I., Ullah, N., Zha, L., Bai, Y., Khan, A., Zhao, T., Che, T., and Zhang, C. (2019). Alteration of gut microbiota in inflammatory bowel disease (IBD): Cause or consequence? IBD treatment targeting the gut microbiome. Pathogens, 8.","DOI":"10.3390\/pathogens8030126"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/apt.12878","article-title":"Systematic review: The role of the gut microbiota in chemotherapy- or radiation-induced gastrointestinal mucositis\u2014Current evidence and potential clinical applications","volume":"40","author":"Touchefeu","year":"2014","journal-title":"Aliment Pharmacol Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"131374","DOI":"10.1016\/j.chemosphere.2021.131374","article-title":"Probiotic intervention mitigates the metabolic disturbances of perfluorobutanesulfonate along the gut-liver axis of zebrafish","volume":"284","author":"Hu","year":"2021","journal-title":"Chemosphere"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1902719","DOI":"10.1080\/19490976.2021.1902719","article-title":"The gut microbiota metabolite capsiate promotes GPX4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis","volume":"13","author":"Deng","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Gu, K., Wu, A., Yu, B., Zhang, T., Lai, X., Chen, J., Yan, H., Zheng, P., Luo, Y., and Luo, J. (2023). Iron overload induces colitis by modulating ferroptosis and interfering gut microbiota in mice. Sci. Total Environ., 905.","DOI":"10.1016\/j.scitotenv.2023.167043"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yang, T., Aquino, V., Lobaton, G.O., Li, H., Colon-Perez, L., Goel, R., Qi, Y., Zubcevic, J., Febo, M., and Richards, E.M. (2019). Sustained captopril-induced reduction in blood pressure is associated with alterations in gut-brain axis in the spontaneously hypertensive rat. J. Am. Heart Assoc., 8.","DOI":"10.1161\/JAHA.118.010721"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"165678","DOI":"10.1016\/j.scitotenv.2023.165678","article-title":"Probiotics ameliorate benzene-induced systemic inflammation and hematopoietic toxicity by inhibiting Bacteroidaceae-mediated ferroptosis","volume":"899","author":"Zhang","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_77","unstructured":"Center for Drug Evaluation and Research (2023, October 21). Product Development Under the Animal Rule. Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/product-development-under-animal-rule."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/17460441.2020.1811671","article-title":"What are the practical, ethical, and pathobiological considerations in the use of minipigs as an animal model in drug discovery for acute radiation syndrome and delayed effects of acute radiation exposure?","volume":"16","author":"Kenchegowda","year":"2021","journal-title":"Expert. Opin. Drug Discov."},{"key":"ref_79","first-page":"65","article-title":"Vascular access port implantation and serial blood sampling in a Gottingen minipig (Sus scrofa domestica) model of acute radiation injury","volume":"50","author":"Moroni","year":"2011","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.ijrobp.2013.04.041","article-title":"The G\u00f6ttingen minipig is a model of the hematopoietic acute radiation syndrome: G-colony stimulating factor stimulates hematopoiesis and enhances survival from lethal total-body gamma-irradiation","volume":"86","author":"Moroni","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Krakau, S., Straub, D., Gourle, H., Gabernet, G., and Nahnsen, S. (2022). nf-core\/mag: A best-practice pipeline for metagenome hybrid assembly and binning. NAR Genom. Bioinform., 4.","DOI":"10.1093\/nargab\/lqac007"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Wood, D.E., Lu, J., and Langmead, B. (2019). Improved metagenomic analysis with Kraken 2. Genome Biol., 20.","DOI":"10.1186\/s13059-019-1891-0"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e12198","DOI":"10.7717\/peerj.12198","article-title":"Struo2: Efficient metagenome profiling database construction for ever-expanding microbial genome datasets","volume":"9","author":"Youngblut","year":"2021","journal-title":"PeerJ"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.7717\/peerj-cs.104","article-title":"Bracken: Estimating species abundance in metagenomics data","volume":"3","author":"Lu","year":"2017","journal-title":"PeerJ Comp. Sci."},{"key":"ref_87","unstructured":"Dabdoub, S.M. (2023, October 21). Kraken-biom: Enabling Interoperative Format Conversion for Kraken Results (Version 1.2). Available online: https:\/\/github.com\/smdabdoub\/kraken-biom."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_89","unstructured":"Bisanz, J.E. (2023, October 21). qiime2R: Importing QIIME2 Artifacts and Associated Data into R Sessions. Available online: https:\/\/github.com\/jbisanz\/qiime2R."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:31:42Z","timestamp":1760106702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,20]]},"references-count":90,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084535"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084535","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,20]]}}}