The Role of NAD⁺ Depletion in the Mechanism 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.

Keywords :

• Cell culture
• Glycolysis
• HD
• Keratinocytes
• NAD⁺
• Niacinamide
• Sulfur mustard
• Toxicology

Abbreviations
SM	=	(sulfur mustard, 2,2′-dichlorodiethyl sulfide)
HEK	=	(human epidermal keratinocytes)
PARP	=	(poly (ADP-ribose) polymerase)

Abbreviations
SM	=	(sulfur mustard, 2,2′-dichlorodiethyl sulfide)
HEK	=	(human epidermal keratinocytes)
PARP	=	(poly (ADP-ribose) polymerase)

Notes

This article is not subject to United States copyright law. Disclaimer: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense, USA.