Alpha-phenyl-N-tert-butylnitrone attenuates hyperoxia-induced lung injury by down-modulating inflammation in neonatal...

This study was done to determine whether alpha -phenyl-N-tert-butylnitrone (PBN), a spin-trapping agent possessing significant anti-inflammatory capabilities, could attenuate hyperoxia-induced lung injury, and if so, whether this protective effect is mediated by the down-modulation of inflammation in neonatal rats. Newborn Sprague-Dawley rat pups were subjected to 14 days of hyperoxia (> 90% oxygen) within 10 hours after birth. PBN treatment, given 100 mg/kg intraperitoneally daily throughout the experiment, significantly attenuated hyperoxia-induced lung pathology, such as decreased radial alveolar count, increased mean linear intercept, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling-positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase that is responsible for superoxide anion production, as evidenced by up-regulation and membrane translocation of p67phox, and the inflammatory responses, such as increased mRNA expression of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta, were also significantly attenuated with PBN treatment. In summary, a spin-trapping agent PBN significantly attenuated hyperoxia-induced lung injury by down-regulating the inflammatory responses in neonatal rats.