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Glutathione synthetic activity in the lungs in newborn guinea pigs
J C Lavoie1, M Spalinger, P Chessex
1Department of Pediatrics and Research Center Hospital Ste-Justine, University of Montréal, 3175 Chemin Côte Sainte-Catherine, Montréal, Québec H3T 1C5, Canada.
Insights
General surgery in newborn guinea pigs increased lung glutathione synthesis and content. This suggests surgical procedures impact lung antioxidant defenses similarly to hyperoxia, highlighting glutathione synthesis as key.
Area of Science:
- Biochemistry
- Neonatal Physiology
- Pulmonary Medicine
Background:
- Glutathione, a critical antioxidant, protects against lung injury.
- Reduced glutathione levels in premature infants with respiratory distress syndrome increase the risk of bronchopulmonary dysplasia.
- Increased glutathione synthetic activity is observed in oxygen-dependent, ventilated neonates.
Purpose of the Study:
- To investigate if a surgical procedure influences lung glutathione levels.
- To determine the role of general surgery in affecting lung glutathione metabolism.
- To compare the effect of surgery on lung glutathione to that of hyperoxia.
Main Methods:
- One-day-old guinea pig pups were divided into surgical and non-surgical groups.
- Lungs were sampled after 4 days to measure glutathione content and enzyme activities.
- Glutathione synthetic activity was assessed in lung tissue.
Main Results:
- A surgical procedure significantly stimulated glutathione synthetic activity (p < 0.02).
- Pulmonary glutathione content increased significantly (p < 0.02) post-surgery.
- Glutathione concentration strongly correlated with synthetic activity (r2 = 0.67).
Conclusions:
- General surgical procedures stimulate lung glutathione synthesis and increase pulmonary glutathione content in this neonatal model.
- The effect of surgery on lung glutathione metabolism resembles that of hyperoxia.
- Glutathione synthetic activity is a primary driver of lung glutathione concentrations, more so than other related enzymes.
Abstract:
Depletion of glutathione, a key antioxidant, accelerates lung injury. Glutathione concentrations are reduced significantly in premature infants with respiratory distress syndrome, leaving them at greater risk of bronchopulmonary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infants was caused by their postsurgical state. Our objective was to evaluate the role of a general surgical procedure as a factor affecting lung glutathione. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a standardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutathione content, activities of gamma-glutamyltranspeptidase, glutathione peroxidase, and reductase as well as the glutathione synthetic activity. The surgical procedure was associated with a specific stimulatory effect limited to glutathione synthetic activity (p < 0.02) leading to an increased (p < 0.02) pulmonary glutathione content. Glutathione concentration was significantly correlated (r2 = 0.67) with the synthetic activity. We concluded that in this animal model an invasive procedure such as a general surgical procedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant of glutathione concentrations than the activities of the other enzymes involved in maintaining glutathione levels.