%0 Journal Article
%T Protective Effects of Beta-3 Adrenoceptor Agonism on Mucosal Integrity in Hyperoxia-Induced Ileal Alterations.
%A Nardini P
%A Zizi V
%A Molino M
%A Fazi C
%A Calvani M
%A Carrozzo F
%A Giuseppetti G
%A Calosi L
%A Guasti D
%A Biagini D
%A Di Francesco F
%A Filippi L
%A Pini A
%J Antioxidants (Basel)
%V 13
%N 7
%D 2024 Jul 18
%M 39061931
%F 7.675
%R 10.3390/antiox13070863
%X Organogenesis occurs in the uterus under low oxygen levels (4%). Preterm birth exposes immature newborns to a hyperoxic environment, which can induce a massive production of reactive oxygen species and potentially affect organ development, leading to diseases such as necrotizing enterocolitis. The β3-adrenoreceptor (β3-AR) has an oxygen-dependent regulatory mechanism, and its activation exerts an antioxidant effect. To test the hypothesis that β3-AR could protect postnatal ileal development from the negative impact of high oxygen levels, Sprague-Dawley rat pups were raised under normoxia (21%) or hyperoxia (85%) for the first 2 weeks after birth and treated or not with BRL37344, a selective β3-AR agonist, at 1, 3, or 6 mg/kg. Hyperoxia alters ileal mucosal morphology, leading to increased cell lipid oxidation byproducts, reduced presence of β3-AR-positive resident cells, decreased junctional protein expression, disrupted brush border, mucin over-production, and impaired vascularization. Treatment with 3 mg/kg of BRL37344 prevented these alterations, although not completely, while the lower 1 mg/kg dose was ineffective, and the higher 6 mg/kg dose was toxic. Our findings indicate the potential of β3-AR agonism as a new therapeutic approach to counteract the hyperoxia-induced ileal alterations and, more generally, the disorders of prematurity related to supra-physiologic oxygen exposure.