Changes in the glutathione system of lung cell lines after treatment with hydrocortisone

• Published in: Archives of toxicology Vol. 78; no. 7; pp. 402 - 409
• Main Author: WALTHER, Udo I
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.07.2004; Springer Nature B.V
• Subjects: Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Antioxidants; Biological and medical sciences; Cell Line; Cell Size - drug effects; Cell Survival; Chlorides - toxicity; Chromatography, Thin Layer; Coloring Agents; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Glutathione - biosynthesis; Glutathione - metabolism; Glutathione Reductase; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - pharmacology; Lung - cytology; Lung - metabolism; Medical sciences; NADH, NADPH Oxidoreductases - metabolism; Pulmonary Alveoli - cytology; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Respiratory distress syndrome; Toxicology; Trypan Blue; Zinc Compounds - toxicity; Corticosteroid; Alveolar type II cell; Glucocorticoids; Respiratory disease; Steroid hormone; Lung; Antiinflammatory agent; Lung fibroblasts; Hydrocortisone; Alveolar epithelial type II cells; Glucocorticoid; In vitro; Cell line; Treatment; Adrenal hormone; Established cell line; Respiratory distress; Cell system; Fibroblast; ARDS; Glutathione
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-004-0557-0

Administration of anti-inflammatory glucocorticoids is a drug option in the therapy of acute respiratory distress syndrome (ARDS), according to present pathophysiological concepts. Surprisingly, glucocorticoids failed to show beneficial effects. This failure is not understood. In this investigation changes in the glutathione system due to hydrocortisone were found to consist of glutathione depletion and lowered glutathione reductase activities in alveolar epithelial type II cells, contrasted with unchanged activities in a fibroblast-like lung cell line. The glutathione system is thought to be the most important cellular antioxidative system and therefore alveolar epithelial type II cells might be more susceptible to oxidative stress after glucocorticoid treatment. As alveolar epithelial type II cells may be important targets in ARDS, because of their functions (stem cells of type I epithelial cells; surfactant synthesis), these changes might provide an explanation for the failure of glucocorticoids. In the present experiments the capability of hydrocortisone-treated alveolar epithelial type II cells to synthesise glutathione was found to be cysteine dependent at physiological concentrations. Transposing this observation to the in vivo situation, it might be expected that glucocorticoid efficacy in ARDS therapy requires co-administration of substances that increase glutathione synthesis, e.g. N-acetylcysteine.