Protection by extracellular glutathione against sulfur mustard induced toxicity in vitro

1. The present study characterizes the role of extracellularly added glutathione in protection against sulfur mustard (HD) toxicity in a macrophage monocyte cell line J774. 2. Toxic effects of HD depend on dose and duration of exposure with an ED50 of 50 and 75 microM for dividing and confluent cells respectively. 3. Exposure to HD, 100-200 microM caused approximately 15% decrease in the cellular glutathione (GSH) content 2 h after exposure, pretreatment with GSH, 0.2-10 mM, elevated cellular GSH approximately x 1.5. 4. GSH pretreatment increased cell viability after HD 2-3-fold. Similar protective effects of GSH treatment were found in a human epidermoid carcinoma cell line (KB). 5. Protection by post treatment with GSH was apparent even 60 min post HD exposure. 6. No protection was afforded when the intracellular GSH concentration was elevated prior to exposure and the extracellular GSH had been washed out. However, GSH depleted cells were more sensitive to HD than normal cells, and were also protected by addition of GSH to the growth medium, although the intracellular GSH content remained low. 7. We conclude that it is essential for the GSH to be present extracellularly in order to protect cells from HD toxicity. 8. Our findings have therapeutic implications in particular for the protection of lungs after inhalation exposure to HD vapor.