β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations

Oxygen level is a key regulator of organogenesis and its modification in postnatal life alters the maturation process of organs, including the intestine, which do not completely develop in utero. The β3-adrenoreceptor (β3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2023-12, Vol.13 (12), p.1755
Main Authors: Filippi, Luca, Nardini, Patrizia, Zizi, Virginia, Molino, Marta, Fazi, Camilla, Calvani, Maura, Carrozzo, Francesco, Cavallaro, Giacomo, Giuseppetti, Giorgia, Calosi, Laura, Crociani, Olivia, Pini, Alessandro
Format: Article
Language:English
Subjects:
Adrenergic beta agonists
Adrenergic receptors
Animals
Antibodies
beta-3 adrenoceptor
beta-3 adrenoceptor agonism
Body weight loss
BRL37344
Catecholamines
Colon
Colon (Anatomy)
Complications and side effects
Enteric nervous system
gut
Health aspects
Hyperoxia
Hypotheses
Hypoxia
Myenteric plexus
Neonates
Neural coding
Organogenesis
Physiological aspects
Premature birth
Proteins
Respiration disorders
Software
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Summary:Oxygen level is a key regulator of organogenesis and its modification in postnatal life alters the maturation process of organs, including the intestine, which do not completely develop in utero. The β3-adrenoreceptor (β3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the β3-AR agonist BRL37344 in a neonatal model of hyperoxia-driven colonic injury. For the first 14 days after birth, Sprague-Dawley rat pups were exposed to ambient oxygen levels (21%) or hyperoxia (85%) and treated daily with BRL37344 at 1, 3, 6 mg/kg or untreated. At the end of day 14, proximal colon samples were collected for analysis. Hyperoxia deeply influences the proximal colon development by reducing β3-AR-expressing cells (27%), colonic length (26%) and mucin production (47%), and altering the neuronal chemical coding in the myenteric plexus without changes in the neuron number. The administration of BRL37344 at 3 mg/kg, but not at 1 mg/kg, significantly prevented these alterations. Conversely, it was ineffective in preventing hyperoxia-induced body weight loss. BRL37344 at 6 mg/kg was toxic. These findings pave the way for β3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom13121755