Nonprotein sulfhydryl alterations in F-344 rats following acute methyl chloride inhalation

Abstract

This study examined the effect of acute methyl chloride (MeCl) inhalation on F-344 rat tissue nonprotein sulfhydryl (NPSH), largely reduced glutathione. Rats were exposed to MeCl concentrations of 1500, 500, or 100 ppm. A 6-hr exposure to 1500 ppm of MeCl decreased the NPSH content of liver, kidney, and lungs to 17, 27, and 30% of control values, respectively, while 500 ppm MeCl lowered the liver, kidney, and lung NPSH to 41, 59, and 55% of control values, respectively, demonstrating a concentration-related effect. Blood NPSH did not differ from controls in either of these groups. No statistically significant changes from controls in tissue or blood NPSH were observed following a 100-ppm MeCl exposure. The extent of tissue NPSH loss was dependent on exposure duration. Liver and kidney NPSH returned to control NPSH concentrations within 8 hr following exposure of 1500 ppm MeCl. Pretreatment of rats with Aroclor-1254 or SKF-525A did not alter the MeCl-induced decrease in tissue NPSH. These data indicate that MeCl reacts extensively with tissue NPSH in vivo in a concentration-related fashion following acute inhalation exposure. The most likely NPSH constituent with which MeCl reacts is reduced glutathione. The finding that blood NPSH was not affected, in contrast to liver, kidney, or lung NPSH, indicates a tissue-specific reaction between MeCl and sulfhydryl groups, a reaction in which the tissue enzyme glutathione- S-alkyltransferase may play a role.