The role of NAD+ depletion in the mechanism of sulfur mustard-induced metabolic injury

Results of our previous studies on the chemical warfare agent sulfur mustard (2,2'-dichlorodiethyl sulfide) suggested that mustard-induced inhibition of glycolysis is not solely a function of NAD(+) depletion. To define the role of NAD(+) in mustard-induced metabolic injury, we examined the effects of mustard niacinamide on energy metabolism in cultured human keratinocytes. Sulfur mustard caused concentration-dependent decreases in viable cell number and ATP content at 24 hours, but not earlier, and time- and concentration-dependent glycolytic inhibition and NAD(+) depletion as early as 4 hours. Niacinamide partially protected NAD(+) levels at all time points, but did not prevent adverse effects on glycolysis, intracellular A TP, or viable cell number. These results support our earlier conclusions and suggest that sulfur mustard may inhibit glycolysis directly.