{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:46:27Z","timestamp":1792097187929,"version":"4.4.0"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Fecal peritonitis induces severe oxidative and inflammatory injury and may involve ferroptosis-related mechanisms. This study investigated the effects of Ferrostatin-1 (Fer-1) on cecal ligation and puncture (CLP)-induced colonic injury, with emphasis on oxidative stress, inflammation, ferroptosis-related alterations, and treatment timing. Thirty-five male Wistar rats were randomly assigned to five groups: Sham, CLP, CLP + dimethyl sulfoxide (DMSO), CLP + Fer-1 (30 min), and CLP + Fer-1 (2 h). Fer-1 (5 mg\/kg, intraperitoneally) was administered after CLP. Biochemical and inflammatory parameters, colonic histopathology, and acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) immunoreactivity were evaluated. CLP induced marked oxidative and inflammatory alterations, increased histopathological damage and ACSL4 immunoreactivity, and decreased GPX4 immunoreactivity (all overall p &lt; 0.001, except total antioxidant status, p = 0.004). Fer-1 treatment generally shifted these alterations toward the sham profile. In exploratory comparisons adjusted for multiple testing, the 2 h group showed lower malondialdehyde, tumor necrosis factor-alpha, and interleukin-6 levels and higher catalase concentrations than the 30 min group (Holm-adjusted p &lt; 0.05). Group-adjusted analyses indicated that the strong pooled correlations were largely attributable to between-group differences. In silico analyses provided complementary hypothesis-generating molecular context. Fer-1 attenuated CLP-induced colonic injury and was associated with favorable oxidative\u2013inflammatory changes and ferroptosis-related ACSL4\/GPX4 alterations. However, the timing findings do not establish an optimal therapeutic window, and direct measures of ferroptotic cell death are required to clarify the contribution of ferroptosis-associated mechanisms.<\/jats:p>","DOI":"10.3390\/cimb48090894","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:41:18Z","timestamp":1788266478000},"page":"894","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ferrostatin-1 Attenuates CLP-Induced Colonic Injury: Associations with Ferroptosis-Related Alterations, Oxidative Stress, Inflammation, and Treatment Timing"],"prefix":"10.3390","volume":"48","author":[{"given":"Mehmet Tolga","family":"Kafadar","sequence":"first","affiliation":[{"name":"Department of General Surgery, Faculty of Medicine, Dicle University, 21280 Diyarbak\u0131r, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"given":"Eda","family":"Y\u0131ld\u0131zhan","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"John, J., Anto, D., Musthafa, S., Moustafa, O., and Zarour, A. (2024). Colonic Perforation in Critically Ill COVID-19 Patients: A Case Series Highlighting Surgical Management and Outcomes. Cureus, 16.","DOI":"10.7759\/cureus.70839"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/01.sla.0000184843.89836.35","article-title":"Complicated diverticulitis: Is it time to rethink the rules?","volume":"242","author":"Chapman","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sartelli, M., Chichom-Mefire, A., Labricciosa, F.M., Hardcastle, T., Abu-Zidan, F.M., Adesunkanmi, A.K., Ansaloni, L., Bala, M., Balogh, Z.J., and Beltran, M.A. (2017). The management of intra-abdominal infections from a global perspective: 2017 WSES guidelines for management of intra-abdominal infections. World J. Emerg. Surg., 12, Erratum in World J. Emerg. Surg.\u00a02017, 12, 36. https:\/\/doi.org\/10.1186\/s13017-017-0141-6.","DOI":"10.1186\/s13017-017-0141-6"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lonsdale, D.O., Shah, R.V., and Lipman, J. (2020). Infection, Sepsis and the Inflammatory Response: Mechanisms and Therapy. Front. Med., 7.","DOI":"10.3389\/fmed.2020.588863"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cicchinelli, S., Pignataro, G., Gemma, S., Piccioni, A., Picozzi, D., Ojetti, V., Franceschi, F., and Candelli, M. (2024). PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020962"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lin, H., Xiong, W., Fu, L., Yi, J., and Yang, J. (2025). Damage-associated molecular patterns (DAMPs) in diseases: Implications for therapy. Mol. Biomed., 6.","DOI":"10.1186\/s43556-025-00305-3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The pathophysiology and treatment of sepsis","volume":"348","author":"Hotchkiss","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bischoff, S.C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.D., Serino, M., Tilg, H., Watson, A., and Wells, J.M. (2014). Intestinal permeability--A new target for disease prevention and therapy. BMC Gastroenterol., 14.","DOI":"10.1186\/s12876-014-0189-7"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1038\/s41556-024-01360-8","article-title":"A guideline on the molecular ecosystem regulating ferroptosis","volume":"26","author":"Dai","year":"2024","journal-title":"Nat. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/nprot.2008.214","article-title":"Immunodesign of experimental sepsis by cecal ligation and puncture","volume":"4","author":"Rittirsch","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Miotto, G., Rossetto, M., Di Paolo, M.L., Orian, L., Venerando, R., Roveri, A., Vu\u010dkovi\u0107, A.M., Bosello Travain, V., Zaccarin, M., and Zennaro, L. (2020). Insight into the mechanism of ferroptosis inhibition by ferrostatin-1. Redox Biol., 28.","DOI":"10.1016\/j.redox.2019.101328"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/j.tips.2023.08.012","article-title":"Beyond ferrostatin-1: A comprehensive review of ferroptosis inhibitors","volume":"44","author":"Scarpellini","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"177","author":"Hurst","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1172\/JCI200318921","article-title":"C-reactive protein: A critical update","volume":"111","author":"Pepys","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.clinbiochem.2014.09.026","article-title":"A novel and automated assay for thiol\/disulphide homeostasis","volume":"47","author":"Erel","year":"2014","journal-title":"Clin. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","article-title":"A new automated colorimetric method for measuring total oxidant status","volume":"38","author":"Erel","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1001\/archsurg.1970.01340280030009","article-title":"Intestinal mucosal lesion in low-flow states. I. A morphological, hemodynamic, and metabolic reappraisal","volume":"101","author":"Chiu","year":"1970","journal-title":"Arch. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Guler, R., Ozden, E., As\u0131r, F., and Gulsun, B. (2025). High-Dose Shilajit Enhances Xenograft-Mediated Bone Regeneration in a Rat Tibial Defect Model: An In Vivo Experimental Study. Life, 15.","DOI":"10.3390\/life15101528"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"A\u015f\u0131r, F., G\u00f6kalp \u00d6zkorkmaz, E., Yal\u00e7\u0131n, M., \u015eahin, F., and Korak, T. (2026). Skimmianine Pretreatment Attenuates Cerebellar Neuroinflammation and Myelin Injury Following Experimental Cerebral Ischemia\u2013Reperfusion. Antioxidants, 15.","DOI":"10.3390\/antiox15060743"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Korak, T., Ayaz, H., and A\u015f\u0131r, F. (2025). Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-\u03b1. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050756"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Korak, T., Bal Albayrak, M.G., Kasap, M., and Akpinar, G. (2025). Thymoquinone and Metabolic Reprogramming in Breast Cancer: A New Dimension From Proteomic Analysis. J. Biochem. Mol. Toxicol., 39.","DOI":"10.1002\/jbt.70124"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"A\u015f\u0131r, F., Erdemci, F., \u00c7ank\u0131r\u0131, Z., Korak, T., Ba\u015faran, S.\u00d6., Kaplan, \u00d6., Y\u00fckselmi\u015f, \u00d6., D\u00f6nmezdil, N., Ayaz, H., and Kaplan, \u015e. (2024). Zonisamide Ameliorated the Apoptosis and Inflammation in Cerebellar Tissue of Induced Alcohol Addiction Animal Model. Life, 14.","DOI":"10.3390\/life14070795"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"A\u015f\u0131r, F., \u00d6zalp, Z., Y\u00fclek, \u00d6.U., Erdemci, F., Korak, T., and Ta\u015f, F. (2024). CITED1 expression in odontogenic cysts. BMC Oral Health, 24.","DOI":"10.1186\/s12903-024-04413-4"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bezzerri, V., Putignani, L., Mantuano, E., Polini, A., Navarini, L., Vomero, M., Corberi, E., Miacci, V., Papuc, P.E., and Schiavone, V. (2025). A Focus on Inflammatory and Bacterial Biomarkers in Secondary Peritonitis. Cells, 14.","DOI":"10.3390\/cells14211653"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hou, Q., Dou, Z., Zhu, L., and Li, B. (2025). Shielding the Gut: Ghrelin and Ferrostatin-1's Protective Role Against Sepsis-Induced Intestinal Ferroptosis. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010077"},{"key":"ref_30","first-page":"1188","article-title":"Role of Nrf2\/GPX4 mediated ferroptosis in intestinal injury in sepsis","volume":"35","author":"Ma","year":"2023","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4551","DOI":"10.1021\/ja411006a","article-title":"Ferrostatins Inhibit Oxidative Lipid Damage and Cell Death in Diverse Disease Models","volume":"136","author":"Skouta","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chom.2018.05.009","article-title":"Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis","volume":"24","author":"Kang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/08923973.2022.2121927","article-title":"Sestrin2 suppresses ferroptosis to alleviate septic intestinal inflammation and barrier dysfunction","volume":"45","author":"Liu","year":"2023","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","article-title":"Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shimizu, J., Murao, A., Nofi, C., Wang, P., and Aziz, M. (2022). Extracellular CIRP Promotes GPX4-Mediated Ferroptosis in Sepsis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.903859"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Van Coillie, S., Van San, E., Goetschalckx, I., Wiernicki, B., Mukhopadhyay, B., Tonnus, W., Choi, S.M., Roelandt, R., Dumitrascu, C., and Lamberts, L. (2022). Targeting ferroptosis protects against experimental (multi)organ dysfunction and death. Nat. Commun., 13, Correction in Nat. Commun.\u00a02025, 16, 8313. https:\/\/doi.org\/10.1038\/s41467-022-28718-6.","DOI":"10.1038\/s41467-025-64122-6"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/894\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:08:37Z","timestamp":1788268117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/9\/894"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":38,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["cimb48090894"],"URL":"https:\/\/doi.org\/10.3390\/cimb48090894","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}