Human premature neonates suffer from
respiratory distress syndrome due to immature lungs and require assisted ventilation with high concentrations of
oxygen. Hyperoxic exposure and/or
antioxidant deficiency causes an increase in the lung levels of
reactive oxygen species (ROS) leading to oxidative stress-induced cellular damage. In this study, we explored the protective role of the nonenzymatic
antioxidant glutathione, by administering
glutathione ethyl ester (GSHEE), in newborn rats exposed to
hyperoxia (>95% FiO(2)). Our results show that GSHEE supplementation (5 mmol/kg/day) prevents mortality in newborn rats exposed to
hyperoxia. We further show that delayed GSHEE supplementation in newborn rats, pre-exposed to
hyperoxia for 4 days, also prevents death. Electron microscopic studies on the lung of GSHEE-treated hyperoxic rats showed normal histology and an absence of the marked swelling and degeneration of mitochondria and lamellar bodies, which are typically observed in the hyperoxic lungs of newborn rats. Furthermore, there were no apparent differences in
weight gain or general appearance/activity among room air and hyperoxic GSHEE-supplemented animals when monitored, post-treatment, in room air for 30 days. Our results show a preventive/therapeutic role of GSHEE supplementation against mortality caused in newborn rats due to hyperoxic exposure, and may further be applicable to a variety of degenerative diseases that are caused as a result of ROS accumulation.