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01-03-2021 | Original Article

Hepatic oxidative injury: role of mitochondrial dysfunction in necrotizing enterocolitis

Authors: Edoardo Bindi, Mashriq Alganabi, George Biouss, Jia Liu, Bo Li, Hiromu Miyake, Rossella Angotti, Agostino Pierro

Published in: Pediatric Surgery International | Issue 3/2021

Abstract

Purpose

Necrotizing enterocolitis (NEC) is a severe neonatal gastrointestinal disease that can cause damage to remote organs. Previous studies have shown that inflammatory and oxidative injury occur in the liver during NEC. Mitochondrial DNA (mtDNA) plays an important role in hepatic injuries of many other diseases. We aimed to investigate the mechanism of mitochondrial dysfunction in hepatic oxidative injury during NEC.

Methods

NEC was induced in C57BL/6 mice (approval: 44032) by hypoxia, gavage feeding with hyperosmolar formula, and lipopolysaccharide administration from postnatal days 5 to 9 (n = 15). Two additional groups with hypoxia only (n = 10) and hypoxia and hyperosmolar formula (n = 13) were also examined. Breastfed pups were used as control (n = 15). Liver was harvested on postnatal day 9. Gene expressions of mtDNA markers cytochrome c oxidase subunit 3 (COX3), cytochrome b (CYTB) and NADH-ubiquinone oxidoreductase chain 1 (ND1) were measured by real-time qPCR. Mitochondrial morphology marker HSP60 and oxidative stress marker NRF2 were detected by immunofluorescence staining and compared between NEC and control. Data were presented as mean ± SD and compared using Student’s t test; p < 0.05 was considered significant.

Results

Gene expression of mtDNA markers (COX3, CYTB, and ND1) were significantly decreased in the liver of NEC mice relative to control, hypoxia alone, and hypoxia with hyperosmolar formula. Immunofluorescence showed depletion of HSP60 indicating decreased mitochondria in NEC liver relative to control. Furthermore, a higher protein expression of NRF2 was observed indicating higher oxidative stress in NEC liver relative to control.

Conclusions

Intestinal injury in experimental NEC leads to a systemic inflammatory response affecting the liver. Hepatic oxidative injury in NEC is characterized by decreased mitochondria and mtDNA depletion. This study provides insight into the mechanism of liver injury in NEC.

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Title: Hepatic oxidative injury: role of mitochondrial dysfunction in necrotizing enterocolitis
Authors: Edoardo Bindi
Mashriq Alganabi
George Biouss
Jia Liu
Bo Li
Hiromu Miyake
Rossella Angotti
Agostino Pierro
Publication date: 01-03-2021
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Surgery International / Issue 3/2021
Print ISSN: 0179-0358
Electronic ISSN: 1437-9813
DOI: https://doi.org/10.1007/s00383-020-04816-8

At a glance: The STEP trials

Springer Medicine

Hepatic oxidative injury: role of mitochondrial dysfunction in necrotizing enterocolitis

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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