Glutathione synthetic activity in the lungs in newborn guinea pigs

Depletion of glutathione, a key antioxidant, accelerates lung injury. Gluta thione concentrations are reduced significantly in premature infants with r espiratory distress syndrome, leaving them at greater risk of bronchopulmon ary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infa nts was caused by their postsurgical state. Our objective was to evaluate t he role of a general surgical procedure as a factor affecting lung glutathi one. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a st andardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutat hione content, activities of gamma-glutamyltranspeptidase, glutathione pero xidase, and reductase as well as the glutathione synthetic activity. The su rgical 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 significa ntly correlated (r(2) = 0.67) with the synthetic activity. We concluded tha t in this animal model an invasive procedure such as a general surgical pro cedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant o f glutathione concentrations than the activities of the ether enzymes invol ved in maintaining glutathione levels.