Alpha-phenyl-N-tert-butylnitrone attenuates hyperoxia-induced lung injury by down-modulating inflammation in neonatal rats.
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.
Chang
Yun Sil
YS
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kim
Yu Jin
YJ
Yoo
Hye Soo
HS
Sung
Dong Kyung
DK
Kim
Soo Yoon
SY
Kang
Saem
S
Park
Won Soon
WS