β3 Adrenoceptor Agonism Prevents Hyperoxia-Induced Colonic Alterations.

Autor: Filippi, Luca, Nardini, Patrizia, Zizi, Virginia, Molino, Marta, Fazi, Camilla, Calvani, Maura, Carrozzo, Francesco, Cavallaro, Giacomo, Giuseppetti, Giorgia, Calosi, Laura, Crociani, Olivia, Pini, Alessandro
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Zdroj: Biomolecules (2218-273X); Dec2023, Vol. 13 Issue 12, p1755, 17p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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