Cathelicidin attenuates hyperoxia-induced lung injury by inhibiting oxidative stress in newborn rats

High concentrations of oxygen administered to newborn infants with respiratory failure increases oxidant stress and leads to lung injury, characterized by decreased alveolar and capillary development. Cathelicidin belongs to an important group of human antimicrobial peptides that exhibit antioxidant activity; its overexpression reduces hyperoxia-induced oxidative stress. This study evaluated the therapeutic effects of cathelicidin in hyperoxia-induced lung injury in newborn rats. Sprague Dawley rat pups were reared in either room air (RA) or hyperoxia (85% O2) and then randomly treated with low-dose (4 mg/kg) and high-dose (8 mg/kg) cathelicidin in 0.05 mL of normal saline (NS) administered intraperitoneally on postnatal days 1–6. The following six groups were obtained: RA + NS, RA + low-dose cathelicidin, RA + high-dose cathelicidin, O2 + NS, O2 + low-dose cathelicidin, and O2 + high-dose cathelicidin. Lungs were harvested for Western blot and histological analyses on postnatal day 7. Compared with the RA-reared rats, the hyperoxia-reared rats exhibited significantly lower body weights, higher mean linear intercept (MLI), lung injury score, interleukin-6, and oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) expression but lower superoxide dismutase 1 (SOD1) and vascular endothelial growth factor (VEGF) protein expression and vascular density. Cathelicidin treatment attenuated hyperoxia-induced lung injury as demonstrated by lower MLI and injury score and higher VEGF expression and vascular density. Cathelicidin attenuated hyperoxia-induced lung injury and caused a decrease in 8-OHdG and SOD1 protein expression, most likely by inhibiting oxidative stress in the lung.