Research progress on the pathological mechanisms and clinical translation of ferroptosis in necrotizing enterocolitis

Jun LUO; Wen-Bin LI

doi:10.7499/j.issn.1008-8830.2507042

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Chinese Journal of Contemporary Pediatrics ›› 2026, Vol. 28 ›› Issue (9) : 1170-1174. DOI: 10.7499/j.issn.1008-8830.2507042

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Research progress on the pathological mechanisms and clinical translation of ferroptosis in necrotizing enterocolitis

Jun LUO ¹ ,
Wen-Bin LI ²

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Abstract

Necrotizing enterocolitis (NEC) is a life-threatening intestinal disease of preterm infants, with a complex pathogenesis involving inflammation, oxidative stress, and cell death. In recent years, ferroptosis, a novel iron-dependent form of programmed cell death, has attracted increasing attention for its role in NEC. This review systematically summarizes the mechanisms of ferroptosis and its relationship with NEC, elucidates its roles in intestinal barrier injury, inflammatory response, and oxidative stress in NEC, and explores potential intervention strategies, aiming to provide new directions for the early diagnosis and treatment of NEC.

Key words

Necrotizing enterocolitis / Ferroptosis / Oxidative stress / Lipid peroxidation / Neonate

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Jun LUO , Wen-Bin LI. Research progress on the pathological mechanisms and clinical translation of ferroptosis in necrotizing enterocolitis[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(9): 1170-1174 https://doi.org/10.7499/j.issn.1008-8830.2507042

References

List( Publishing order | Descend order by publishing year | Descend order by cited within ) Chart analysis

[1]	Klerk DH, van Varsseveld OC, Offringa M, et al. Core outcome set for necrotizing enterocolitis treatment trials[J]. Pediatrics, 2024, 153(6): e2023065619. DOI: 10.1542/peds.2023-065619 . https://www.ncbi.nlm.nih.gov/pubmed/38726575 Cited in this article [1]

[2]	Gitau K, Ochieng R, Limbe M, et al. The incidence and modifiable risk factors for necrotizing enterocolitis in preterm infants: a retrospective cohort study[J]. J Matern Fetal Neonatal Med, 2023, 36(2): 2253351. DOI: 10.1080/14767058.2023.2253351 . https://www.ncbi.nlm.nih.gov/pubmed/37648650

[3]

Palleri

, Svenningsson

, Markasz

, et al. The incidence of necrotizing enterocolitis and late-onset sepsis during the COVID-19 pandemic in Sweden: a population-based cohort study[J]. Neonatology, 2024, 121(3): 336-341. PMCID: PMC11152026. DOI: 10.1159/000536570 .

https://www.ncbi.nlm.nih.gov/pubmed/38442693

Cited in this article [1]

[4]

Qian

, Zhang

, Zhu

, et al. Necrotizing enterocolitis in low birth weight infants in China: mortality risk factors expressed by birth weight categories[J]. Pediatr Neonatol, 2017, 58(6): 509-515. DOI: 10.1016/j.pedneo.2016.10.004 .

https://www.ncbi.nlm.nih.gov/pubmed/28528756

Cited in this article [1]

[5]

Zhang

, Xie

, Qu

, et al. Digging deeper into necrotizing enterocolitis: bridging clinical, microbial, and molecular perspectives[J]. Gut Microbes, 2025, 17(1): 2451071. PMCID: PMC12128673. DOI: 10.1080/19490976.2025.2451071 .

https://www.ncbi.nlm.nih.gov/pubmed/39826099

Cited in this article [1]

[6]

Dang

, Zhang

, Meng

, et al. Integrative analysis links ferroptosis to necrotizing enterocolitis and reveals the role of ACSL4 in immune disorders[J]. iScience, 2022, 25(11): 105406. PMCID: PMC9638783. DOI: 10.1016/j.isci.2022.105406 .

https://www.ncbi.nlm.nih.gov/pubmed/36353724

Cited in this article [2]

[7]

Luo

, Zeng

, Chen

, et al. Vitamin E and GPX4 cooperatively protect treg cells from ferroptosis and alleviate intestinal inflammatory damage in necrotizing enterocolitis[J]. Redox Biol, 2024, 75: 103303. PMCID: PMC11372871. DOI: 10.1016/j.redox.2024.103303 .

https://www.ncbi.nlm.nih.gov/pubmed/39137584

Cited in this article [3]

[8]	Cui S, Ye J. Ferroptosis: the demise of cells through phospholipid peroxidation[J]. Adv Sci (Weinh), 2026,13(23):e24387. PMCID: PMC13104129. DOI: 10.1002/advs.202524387 . https://www.ncbi.nlm.nih.gov/pubmed/41858270 Cited in this article [1]

[9]	Qiu B, Zandkarimi F, Bezjian CT, et al. Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis[J]. Cell, 2024, 187(5): 1177-1190.e18. PMCID: PMC10940216. DOI: 10.1016/j.cell.2024.01.030 . https://www.ncbi.nlm.nih.gov/pubmed/38366593 Cited in this article [1]

[10]	Gao G, Li J, Zhang Y, et al. Cellular iron metabolism and regulation[J]. Adv Exp Med Biol, 2019, 1173: 21-32. DOI: 10.1007/978-981-13-9589-5_2 . https://www.ncbi.nlm.nih.gov/pubmed/31456203 Cited in this article [1]

[11]

Creoli

, Di Paola

, Tarallo

, et al. Effects of CB2 receptor modulation on macrophage polarization in pediatric inflammatory bowel disease[J]. Int J Mol Sci, 2025, 26(8): 3720. PMCID: PMC12027514. DOI: 10.3390/ijms26083720 .

https://www.ncbi.nlm.nih.gov/pubmed/40332343

Cited in this article [2]

[12]	Yu Y, Yan Y, Niu F, et al. Ferroptosis: a cell death connecting oxidative stress, inflammation and cardiovascular diseases[J]. Cell Death Discov, 2021, 7(1): 193. PMCID: PMC8313570. DOI: 10.1038/s41420-021-00579-w . https://www.ncbi.nlm.nih.gov/pubmed/34312370 Cited in this article [1]

[13]	Liu W, Wu Y, Zhang N, et al. Disordered maternal and fetal iron metabolism occurs in preterm births in human[J]. Dis Markers, 2022, 2022: 1664474. PMCID: PMC9423993. DOI: 10.1155/2022/1664474 . https://www.ncbi.nlm.nih.gov/pubmed/36046373 Cited in this article [1]

[14]	Chen C, Wu ZH, Lu XJ, et al. BRIP1 induced ferroptosis to inhibit glioma cells and was associated with increased oxidative stress[J]. Discov Med, 2024, 36(190): 2264-2273. DOI: 10.24976/Discov.Med.202436190.208 . https://www.ncbi.nlm.nih.gov/pubmed/39600281 Cited in this article [1]

[15]

Ren

, Zhu

, Li

, et al. Lespedeza bicolor Turcz. honey prevents inflammation response and inhibits ferroptosis by Nrf2/ HO-1 pathway in DSS-induced human caco-2 cells[J]. Antioxidants (Basel), 2024, 13(8): 900. PMCID: PMC11351236. DOI: 10.3390/antiox13080900 .

https://www.ncbi.nlm.nih.gov/pubmed/39199146

Cited in this article [1]

[16]

Bian

, Wei

, Wang

. Carthamin yellow alleviates dextran sodium sulfate-induced ulcerative colitis by repairing the intestinal barrier and activating the Nrf2/GPX4 axis[J]. Int Immunopharmacol, 2024, 141: 113020. DOI: 10.1016/j.intimp.2024.113020 .

https://www.ncbi.nlm.nih.gov/pubmed/39208524

Cited in this article [1]

[17]	Gan B. ACSL4, PUFA, and ferroptosis: new arsenal in anti-tumor immunity[J]. Signal Transduct Target Ther, 2022, 7(1): 128. PMCID: PMC9033814. DOI: 10.1038/s41392-022-01004-z . https://www.ncbi.nlm.nih.gov/pubmed/35459217 Cited in this article [1]

[18]

Zhang

, Jing

, He

, et al. Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis[J]. Immunity, 2025, 58(3): 683-700.e10. DOI: 10.1016/j.immuni.2025.02.003 .

https://www.ncbi.nlm.nih.gov/pubmed/40023163

Cited in this article [1]

[19]	Yang S, Wei X, Zhong Y, et al. Programmed death of intestinal epithelial cells in neonatal necrotizing enterocolitis: a mini-review[J]. Front Pediatr, 2023, 11: 1199878. PMCID: PMC10277470. DOI: 10.3389/fped.2023.1199878 . https://www.ncbi.nlm.nih.gov/pubmed/37342533 Cited in this article [1]

[20]

Chen

, Xu

, Zhang

, et al. Ferroptosis inhibition mitigates glyphosate-induced inflammation and blood-milk barrier disruption in bovine mammary epithelial cells[J]. Food Chem Toxicol, 2026, 209: 115904. DOI: 10.1016/j.fct.2025.115904 .

https://www.ncbi.nlm.nih.gov/pubmed/41421653

Cited in this article [1]

[21]

Hou

, Li

, Chen

, et al. Naringenin alleviates intestinal ischemia/reperfusion injury by inhibiting ferroptosis via targeting YAP/STAT3 signaling axis[J]. Phytomedicine, 2024, 135: 156095. DOI: 10.1016/j.phymed.2024.156095 .

https://www.ncbi.nlm.nih.gov/pubmed/39383632

Cited in this article [1]

[22]	Yang Y, Wang Y, Guo L, et al. Interaction between macrophages and ferroptosis[J]. Cell Death Dis, 2022, 13(4):355.PMCID: PMC9013379. DOI: 10.1038/s41419-022-04775-z . https://www.ncbi.nlm.nih.gov/pubmed/35429990 Cited in this article [1]

[23]

Wang

, He

, Liang

, et al. Huangqin decoction alleviates chemotherapy-induced intestinal injury by inhibiting ferroptosis via modulation of P53/SLC7A11/GPX4 pathway[J]. J Ethnopharmacol, 2025, 351: 120135. DOI: 10.1016/j.jep.2025.120135 .

https://www.ncbi.nlm.nih.gov/pubmed/40513923

Cited in this article [1]

[24]	Chen Y, Chen W, Dai Y, et al. Human breast milk-derived phospholipid DOPE ameliorates intestinal injury associated with NEC by inhibiting ferroptosis[J]. Food Funct, 2024, 15(21): 10811-10822. DOI: 10.1039/d4fo03904a . https://www.ncbi.nlm.nih.gov/pubmed/39403969 Cited in this article [2]

[25]	Akduman H, Tayman C, Korkmaz V, et al. Astaxanthin reduces the severity of intestinal damage in a neonatal rat model of necrotizing enterocolitis[J]. Am J Perinatol, 2022, 39(16): 1820-1827. DOI: 10.1055/s-0041-1727156 . https://www.ncbi.nlm.nih.gov/pubmed/33853144 Cited in this article [1]

[26]	Gershner GH, Hunter CJ. Redox chemistry: implications for necrotizing enterocolitis[J]. Int J Mol Sci, 2024, 25(15): 8416. PMCID: PMC11312856. DOI: 10.3390/ijms25158416 . https://www.ncbi.nlm.nih.gov/pubmed/39125983 Cited in this article [1]

[27]

Golubkova

, Leiva

, Snyder

, et al. Response of the glutathione (GSH) antioxidant defense system to oxidative injury in necrotizing enterocolitis[J]. Antioxidants (Basel), 2023, 12(7): 1385. PMCID: PMC10376622. DOI: 10.3390/antiox12071385 .

https://www.ncbi.nlm.nih.gov/pubmed/37507924

Cited in this article [1]

[28]

Shen

, Chen

, Tou

. Inhibition of ferroptosis in inflammatory macrophages alleviates intestinal injury in neonatal necrotizing enterocolitis[J]. Cell Death Discov, 2025, 11(1):365. PMCID:PMC1232.5787. DOI: 10.1038/s41420-025-02665-9 .

https://www.ncbi.nlm.nih.gov/pubmed/40764334

Cited in this article [1]

[29]

Elgenidy

, Atef Abdelsattar Ibrahim

, Elmozugi

, et al. Efficacy of melatonin for treatment and prevention of neonatal necrotizing enterocolitis: a systematic review[J]. Naunyn Schmiedebergs Arch Pharmacol, 2025, 398(5): 4947-4955. DOI: 10.1007/s00210-024-03681-9 .

https://www.ncbi.nlm.nih.gov/pubmed/39708100

Cited in this article [1]

[30]

Fan

, Chang

, Tian

, et al. Methane saline suppresses ferroptosis via the Nrf2/HO-1 signaling pathway to ameliorate intestinal ischemia-reperfusion injury[J]. Redox Rep, 2024, 29(1): 2373657. PMCID: PMC11259071. DOI: 10.1080/13510002.2024.2373657 .

https://www.ncbi.nlm.nih.gov/pubmed/39023011

Cited in this article [1]

[31]	Yuan L, Wang Y, Li N, et al. Mechanism of action and therapeutic implications of Nrf2/HO-1 in inflammatory bowel disease[J]. Antioxidants (Basel), 2024, 13(8): 1012. PMCID: PMC11351392. DOI: 10.3390/antiox13081012 . https://www.ncbi.nlm.nih.gov/pubmed/39199256 Cited in this article [1]

[32]

Zhang

, Jin

, Hu

, et al. Silencing miR-155-5p expression improves intestinal damage through inhibiting inflammation and ferroptosis in necrotizing enterocolitis[J]. Heliyon, 2024, 10(17): e37087. PMCID: PMC11402723. DOI: 10.1016/j.heliyon.2024.e37087 .

https://www.ncbi.nlm.nih.gov/pubmed/39286078

Cited in this article [1]

[33]

Gao

, Wang

, Fu

, et al. N-acetylcysteine alleviates necrotizing enterocolitis by depressing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells[J]. Inflammation, 2025, 48(1): 464-482. PMCID: PMC11807027. DOI: 10.1007/s10753-024-02068-5 .

https://www.ncbi.nlm.nih.gov/pubmed/39037665

Cited in this article [1]