The Role of NAD+ Depletion in the Mechanisms of Sulfur Mustard-Induced Metabolic Injury

Abstract

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.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2008
Accession Number
ADA502030

Entities

People

  • Margaret E. Martens
  • William J. Smith

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Cell Count
  • Cell Physiological Processes
  • Cells
  • Chemical Warfare
  • Chemical Warfare Agents
  • Culture Techniques
  • Endothelial Cells
  • Epithelial Cells
  • Glycolysis
  • Inhibition
  • Inhibitors
  • Materials
  • Metabolism
  • Regression Analysis
  • Rodents
  • Statistical Analysis

Fields of Study

  • Biology

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