Hyperoxia-
hypoxia exposure is a proposed cause of alveolar developmental arrest in
bronchopulmonary dysplasia in preterm infants, where mitochondrial
reactive oxygen species and oxidative stress vulnerability are increased. The
aryl hydrocarbon receptor (AhR) is one of the main activators of the
antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of
indole-3-carbinol (I3C) protects rat pups from
hyperoxia-
hypoxia-induced
lung injury. To assess the activation of
protein-encoding genes related to the AhR signaling pathway (
Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and
mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of
fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the
hyperoxia-
hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to
hyperoxia-
hypoxia, an RAC recovery was observed, and the
fibrosis index was similar to that of the unexposed control group. A
cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup's lungs and hence attenuates lung damage caused by
hyperoxia-
hypoxia exposure in newborns.