Protective effects of N-acetylcysteine and combined vitamin E and C therapy in hyperoxia-induced lung injury in neonatal rats

Background Hyperoxia-induced lung injury is a key contributor to the development of bronchopulmonary dysplasia in preterm infants, primarily through oxidative stress and impaired antioxidant defense mechanisms. Objective To evaluate the protective effects of N-acetylcysteine (NAC) and combined vitamin E and C therapy on oxidative stress, antioxidant capacity, and lung histopathology in a neonatal rat model of hyperoxia-induced lung injury. Methods A total of 36 neonatal rats were randomly assigned to four groups: control (room air, n = 9), hyperoxia ( n = 9), hyperoxia + NAC ( n = 8), and hyperoxia + vitamin E + C ( n = 10). Hyperoxia exposure (90% ± 10% O 2 ) was maintained from postnatal days 3–14. Treatments were administered intraperitoneally (NAC 150 mg/kg/day, vitamin E 25 IU/day, vitamin C 1 mg/kg/day). Oxidative stress parameters (TOS, OSI, and LOOH), antioxidant markers (TAS, paraoxonase, and arylesterase), and histopathological findings were evaluated in serum and lung tissue. Results Hyperoxia significantly increased oxidative stress markers, with higher TOS levels observed in both serum and lung tissue compared to the control group ( p < 0.001). NAC and vitamin E + C treatments significantly increased TAS levels compared to the hyperoxia group ( p < 0.05). Serum OSI levels were significantly reduced in both treatment groups ( p = 0.002 and p = 0.032). Additionally, arylesterase levels were significantly higher in the vitamin group compared to all other groups ( p < 0.001). Histopathological evaluation demonstrated reduced inflammatory cell infiltration and lower fibrosis scores in the treatment groups. Conclusion N-acetylcysteine and combined vitamin E and C therapy attenuate hyperoxia-induced lung injury by reducing oxidative stress and improving lung histopathology in neonatal rats. These findings support antioxidant strategies as adjunctive approaches for BPD-related lung injury.