Protection by extracellular glutathione against sulfur mustard induced toxicity in vitro

The present study characterizes the role of extracellularly added glutathio ne in protection against sulfur mustard (HD) toxicity in a macrophage monoc yte cell line J774. 2 Toxic effects of HD depend on dose and duration of exposure with an ED50 of 50 and 75 mu M for dividing and confluent cells respectively. 3 Exposure to HD, 100-200 mu M caused similar to 15% decrease in the cellul ar glutathione (GSH) content 2 h after exposure, pretreatment with GSH, 0.2 -10 mM, elevated cellular GSH similar to x 1.5. 4 GSH pretreatment increased cell viability after HD 2-3-fold. Similar prot ective 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 ex posure. 6 No protection was afforded when the intracellular GSH concentration was e levated prior to exposure and the extracellular GSH had been washed out. Ho wever, 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 i ntracellular GSH content remained low. 7 We conclude that it is essential for the GSH to be present extracellularl y in order to protect cells from HD toxicity. 8 Our findings have therapeutic implications in particular far the protecti on of lungs after inhalation exposure to HD vapor.