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Glutathione ethyl ester supplementation prevents mortality in newborn rats exposed to hyperoxia
1Perinatology Center, Department of Pediatrics, New York Hospital-Cornell Medical Center, New York, NY, USA. rsinghal@med.cornell.edu
Insights
Glutathione ethyl ester (GSHEE) protects newborn rats from death caused by high oxygen exposure. This antioxidant treatment also prevents lung cell damage and may help treat other diseases linked to reactive oxygen species (ROS).
Area of Science:
- Biomedical Science
- Neonatal Research
- Oxidative Stress Biology
Background:
- Premature neonates require oxygen therapy, increasing risk of lung injury from hyperoxia.
- Hyperoxia and antioxidant deficiency elevate reactive oxygen species (ROS), causing cellular damage in neonatal lungs.
- Glutathione is a key nonenzymatic antioxidant crucial for cellular protection.
Purpose of the Study:
- To investigate the protective effects of glutathione ethyl ester (GSHEE) against hyperoxia-induced mortality and lung damage in newborn rats.
- To determine if GSHEE administration can be both preventive and therapeutic in a neonatal hyperoxia model.
- To assess the long-term impact of GSHEE treatment on the general health of rats post-hyperoxia exposure.
Main Methods:
- Newborn rats were exposed to hyperoxia (>95% FiO2) and treated with GSHEE (5 mmol/kg/day).
- Delayed GSHEE treatment was administered to rats after 4 days of hyperoxia.
- Lung histology was examined using electron microscopy; animal weight, appearance, and activity were monitored for 30 days post-treatment.
Main Results:
- GSHEE supplementation significantly prevented mortality in newborn rats exposed to hyperoxia.
- Delayed GSHEE administration also proved effective in preventing death in hyperoxia-exposed rats.
- Electron microscopy revealed normal lung histology and preserved mitochondrial/lamellar body structure in GSHEE-treated rats, unlike untreated hyperoxic controls.
- No significant differences in weight gain or general activity were observed between treated and control groups after recovery in room air.
Conclusions:
- GSHEE demonstrates significant preventive and therapeutic potential against hyperoxia-induced mortality in neonatal rats.
- GSHEE protects lung tissue from oxidative stress-induced damage, preserving cellular structures.
- These findings suggest GSHEE may be a valuable therapeutic agent for neonatal respiratory distress and other ROS-related degenerative diseases.
Abstract:
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.