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 ATP, or viable cell number. These results support our earlier conclusions and suggest that sulfur mustard may inhibit glycolysis directly.
Martens
Margaret E
ME
Physiology & Immunology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5400, USA. margaret.a.martens@us.army.mil
Smith
William J
WJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000172:deficiency / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology*; D013997:Time Factors; D014803:Vitamin B Complex / Q000494:pharmacology*
D002619:Chemical Warfare Agents; D009243:NAD; D014803:Vitamin B Complex; D009536:Niacinamide; D000255:Adenosine Triphosphate; D005947:Glucose; D009151:Mustard Gas