The administration of a pre-digested fat-enriched formula prevents necrotising enterocolitis-induced lung injury in mice

Abstract

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurity that typically develops after the administration of infant formula, suggesting a link between nutritional components and disease development. One of the most significant complications that develops in patients with NEC is severe lung injury. We have previously shown that the administration of a nutritional formula that is enriched in pre-digested triglycrides that do not require lipase action can significantly reduce the severity of NEC in a mouse model. We now hypothesize that this 'pre-digested fat system (PDF)' may reduce NEC-associated lung injury. In support of this hypothesis, we now show that rearing newborn mice on a nutritional formula based on the 'pre-digested fat (PDF) system’ promotes lung development, as evidenced by increased tight junctions and surfactant protein expression. Mice who were administered this 'PDF fat system’ were significantly less vulnerable to the development of NEC-induced lung inflammation, and the administration of the 'PDF fat system’ conferred lung protection. In seeking to define the mechanisms involved, the administration of the PDF system’ significantly enhanced lung maturation and reduced the production of reactive oxygen species (ROS). These findings suggest that the PDF system protects the development of NEC-induced lung injury through effects on lung maturation and reduced reactive oxygen species in the lung, and also increase lung maturation in non-NEC mice.

Pharmacologic Toll-like receptor 4 inhibition skews toward a favorable A1/A2 astrocytic ratio improving neurocognitive outcomes following traumatic brain injury

“…Data were analyzed for statistical significance by ordinary one-way analysis of variance followed by Tukey's multiple comparison test or unpaired t test. A power analysis was performed to calculate sample size according to our recent publication, 16 using an effect size of twofold for gene expression. The SD for each of these parameters was based on our previously published studies, 17,18 and we accepted a significance (type 1 error) of 5% ( p = 0.05), the probability of finding an effect of 80%, and an attrition rate based on prior studies of 10%.…”

Neutrophilic Inflammation and Reactive Oxygen Species Production Promotes Necrotizing Enterocolitis induced Lung Injury in Mice

“…In addition, 20µl of NAC (25 mg/kg) in total was directly instilled through the nasal cavity, 4 times a day, 5µl each time, for 4 days. The modeling method of the NEC + PBS group was the same as that of the NEC group, and the same dose of PBS as NAC was administered intranasally every day [13].…”

“…Neonatal lung disease is thought to develop with the production of ROS, which causes severe cellular damage, leading to lung cell death and alveolar damage. In addition, lung injury during other in ammatory processes often involves the accumulation of ROS [13]. After the recruitment and chemotaxis migration of neutrophils in the in ammatory area, neutrophils can remove pathogenic microorganisms by releasing ROS, phagocytosis, degranulation, NETs, and other mechanisms.…”

“…NAC can Alleviate Intestine and Lung Tissue Damage in NEC Group Mice by the Keap1-Nrf2 Pathway NAC, or N-acetyl-L-cysteine, is a redox scavenger that reduces ROS release [13]. Clinically, NAC is a mucolytic agent, with a strong phlegm-dissolving effect.…”

“…It has been found that inhibiting the NETs formation of neutrophils in NEC mice can moderate their intestinal damage [12]. Neonatal lung disease was thought to be accompanied by the production of ROS, which can damage lung tissues [13]. However, there is no report on the role of the ROS release function of neutrophils in NEC lung injury.…”