Antioxidative effects of uridine in a neonatal rat model of hyperoxic brain injury.

BACKGROUND/AIM Premature birth is a major problem that results in increased risk of mortality and morbidity. Management of such infants consists of supraphysiological oxygen therapy, which affects brain development due, in part, to the deterioration caused by reactive oxygen species (ROS). We showed previously that exogenously-administered uridine provides neuroprotection in a neonatal rat model of hyperoxic brain injury. Hence, the aim of the present study was to investigate effects of uridine on ROS in the same setting. MATERIALS AND METHODS Hyperoxic brain injury was induced by subjecting total 53 six-day-old rat pups to 80% oxygen (Hyperoxia group) for a period of 48 hours. Pups in Normoxia group continued breathing room air (21% oxygen). Normoxia+saline or hyperoxia + saline or hyperoxia + uridine100 mg/kg or hyperoxia + uridine300 mg/kg or hyperoxia + uridine500 mg/kg was injected intraperitoneally (i. p.) 15 minutes prior to hyperoxia procedure. Pups were decapitated and brains were homogenized to analyze Superoxide Dismutase (SOD), Glutathione Peroxidase (GSH-Px), Myeloperoxidase (MPO) and Malondialdehyde (MDA) enzymes as well as DJ-1 (Protein deglycase DJ-1), an oxidative stress sensitive protein. RESULTS Hyperoxia-induced may cause overproduction of oxygen radicals and the oxidant / antioxidant balance may be disturbed in the brain. Brain MPO and MDA levels were significantly increased in saline-receiving pups exposed to hyperoxia. Brain SOD and GSH-Px levels were significantly decreased in saline-receiving pups exposed to hyperoxia. Our results showed that uridine administration prevented the hyperoxia-induced decrease in SOD and GSH-Px while counteracting the hyperoxia-induced increase in MPO and MDA in a dose-dependent manner. Uridine also increased DJ-1 levels in brains of rat pups subjected to hyperoxia. CONCLUSION These data suggest that uridine exhibits antioxidative properties which may mediate the protective effects of uridine in a neonatal rat model of hyperoxic brain injury.