1. Mitochondrial DNA: A Biomarker of Disease Severity in Necrotizing Enterocolitis
- Author
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Rossella Angotti, Maarten Janssen Lok, Mashriq Alganabi, Edoardo Bindi, Haitao Zhou, Agostino Pierro, and Bo Li
- Subjects
medicine.medical_specialty ,Lipopolysaccharide ,Ileum ,DNA, Mitochondrial ,Severity of Illness Index ,Gastroenterology ,Proinflammatory cytokine ,Random Allocation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Enterocolitis, Necrotizing ,030225 pediatrics ,Internal medicine ,Animals ,Medicine ,Interleukin 6 ,Enterocolitis ,biology ,business.industry ,Hypoxia (medical) ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Animals, Newborn ,chemistry ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Necrotizing enterocolitis ,Disease Progression ,biology.protein ,Cytokines ,Surgery ,Tumor necrosis factor alpha ,medicine.symptom ,business ,Biomarkers - Abstract
Introduction There is a need to develop sensitive markers to diagnose or monitor the severity of intestinal damage in necrotizing enterocolitis (NEC). Mitochondrial deoxyribonucleic acid (mtDNA) is increased in the intestine and blood of adults in response to intestinal ischemia and can trigger secondary organ damage. We hypothesize that mtDNA is increased during experimental NEC and that mtDNA levels are correlated to the degree of intestinal injury. Materials and Methods NEC was induced in C57BL/6 mice (n = 18) (approval: 44032) by gavage feeding with hyperosmolar formula, hypoxia, and lipopolysaccharide administration from postnatal day (P) 5 to 9. Breastfed pups served as control (n = 15). Blood was collected by cardiac puncture and terminal ileum was harvested on P9. Reverse transcription quatitative polymerase chain reaction was used to measure mtDNA (markers COX3, CYTB, ND1) and inflammatory cytokines (interleukin 6 [IL-6] and tumor necrosis factor-α[TNF-α]) in blood and ileum. Intestinal injury was scored blindly by four investigators and classified as no/minor injury (score 0 or 1) or NEC (score ≥2). Results mtDNA is significantly increased in gut and blood of NEC mice (p Conclusion Following NEC intestinal injury, mtDNA is released from the intestine into circulation. The blood level of mtDNA is related to the degree of intestinal injury. mtDNA can be a novel marker of intestinal injury and can be useful for monitoring the progression of NEC.
- Published
- 2019