Journal article
Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines
Frontiers in pediatrics, Vol.12, 1387171
04/01/2024
DOI: 10.3389/fped.2024.1387171
PMCID: PMC11043547
PMID: 38665380
Abstract
Introduction Meconium ileus (MI) is a life-threatening obstruction of the intestines affecting ∼15% of newborns with cystic fibrosis (CF). Current medical treatments for MI often fail, requiring surgical intervention. MI typically occurs in newborns with pancreatic insufficiency from CF. Meconium contains mucin glycoprotein, a potential substrate for pancreatic enzymes or mucolytics. Our study aim was to determine whether pancreatic enzymes in combination with mucolytic treatments dissolve obstructive meconium using the CF pig model. Methods We collected meconium from CF pigs at birth and submerged it in solutions with and without pancreatic enzymes, including normal saline, 7% hypertonic saline, and the reducing agents N-acetylcysteine (NAC) and dithiothreitol (DTT). We digested meconium at 37 °C with agitation, and measured meconium pigment release by spectrophotometry and residual meconium solids by filtration. Results and discussion In CF pigs, meconium appeared as a solid pigmented mass obstructing the ileum. Meconium microscopically contained mucus glycoprotein, cellular debris, and bile pigments. Meconium fragments released pigments with maximal absorption at 405 nm after submersion in saline over approximately 8 h. Pancreatic enzymes significantly increased pigment release and decreased residual meconium solids. DTT did not improve meconium digestion and the acidic reducing agent NAC worsened digestion. Pancreatic enzymes digested CF meconium best at neutral pH in isotonic saline. We conclude that pancreatic enzymes digest obstructive meconium from CF pigs, while hydrating or reducing agents alone were less effective. This work suggests a potential role for pancreatic enzymes in relieving obstruction due to MI in newborns with CF.
Details
- Title: Subtitle
- Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines
- Creators
- Gopinathan Gangadharan Nambiar - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, United StatesSussette Gonzalez Szachowicz - Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA, United StatesChristian F. Zirbes - University of IowaJared J. Hill - Department of Pediatrics, University of Iowa, Iowa City, IA, United StatesLinda S. Powers - University of IowaDavid K. Meyerholz - University of IowaIan M. Thornell - University of IowaDavid A. Stoltz - University of IowaAnthony J. Fischer - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in pediatrics, Vol.12, 1387171
- Publisher
- Frontiers Media S.A
- DOI
- 10.3389/fped.2024.1387171
- PMID
- 38665380
- PMCID
- PMC11043547
- ISSN
- 2296-2360
- Language
- English
- Date published
- 04/01/2024
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Orthopedics and Rehabilitation; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Internal Medicine
- Record Identifier
- 9984586359402771
Metrics
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