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 beta 3-adrenoreceptor (beta 3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the beta 3-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 beta 3-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 beta 3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders.

β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations / Filippi, Luca; Nardini, Patrizia; Zizi, Virginia; Molino, Marta; Fazi, Camilla; Calvani, Maura; Carrozzo, Francesco; Cavallaro, Giacomo; Giuseppetti, Giorgia; Calosi, Laura; Crociani, Olivia; Pini, Alessandro. - In: BIOMOLECULES. - ISSN 2218-273X. - ELETTRONICO. - 13:(2023), pp. 1755.0-1755.0. [10.3390/biom13121755]

β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations

Filippi, Luca;Nardini, Patrizia;Zizi, Virginia;Molino, Marta;Fazi, Camilla;Calvani, Maura;Carrozzo, Francesco;Calosi, Laura;Crociani, Olivia;
2023

Abstract

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 beta 3-adrenoreceptor (beta 3-AR) is expressed in the colon and has an oxygen-dependent regulatory mechanism. This study shows the effects of the beta 3-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 beta 3-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 beta 3-AR pharmacological targeting as a therapeutic option for diseases caused by hyperoxia-impaired development, typical prematurity disorders.
2023
13
0
0
Goal 3: Good health and well-being
Filippi, Luca; Nardini, Patrizia; Zizi, Virginia; Molino, Marta; Fazi, Camilla; Calvani, Maura; Carrozzo, Francesco; Cavallaro, Giacomo; Giuseppetti, ...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1357480
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