Pathogenesis of 2,2'-dichlorodiethyl sulfide in hairless guinea pigs.
Developing skin lesions on hairless guinea pigs due to 2,2'-dichlorodiethyl sulfide (sulfur mustard, HD) exposure were examined to determine the time course for the appearance of histopathologic markers in relationship to skin NAD+ and NADP+ content after HD exposure. Hairless guinea pig skin was exposed to HD for 8 min by means of a vapor cup. Skin punches were taken at 1, 2, 4, 8, 12, 16, 20 and 24 h after HD exposure. Intracellular edema (IE) appeared at 2 h and increased steadily over 24 h. Epidermal necrosis (EN) and pustular epidermatitis (PE) developed at 8 h and reached a maximum at 16 h. Follicular necrosis (FN) appeared at 8 h and increased up to 24 h. Microvesicles (MV) developed between 12-16 h reaching a maximum at 24 h. Niacinamide (750 mg/kg, ip) pretreatment (30-min) reduced the incidence of MV (40%) and FN (45%) at 24 h, but did not reduce IE, EN, or PE. In all animals, skin NAD+ content decreased to a minimum (20% of control) at 16 h, but NAD+ decreases did not precede microvesicle formation. Skin NADP+ content increased (260%) between 1-2 h and returned to control at 4 h. Skin cell NADP+ increases may be indicative of an early phase of cellular oxidative stress that may contribute to HD-induced dermal pathogenesis. Since NAD+ reductions did not precede microvesication and NAM-induced increases in NAD+ content did not delay or reduce early cellular alterations, the contributory role of NAD+ to microvesicle formation may be limited and other biochemical changes should be investigated.
Yourick
J J
JJ
U.S. Army Medical Research Institute of Chemical Defense, Applied Pharmacology Branch, Aberdeen Proving Ground, MD 21010-5425.
Dawson
J S
JS
Benton
C D
CD
Craig
M E
ME
Mitcheltree
L W
LW
D000818:Animals; D001768:Blister / Q000139:chemically induced; D004347:Drug Interactions; D006168:Guinea Pigs; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000473:pathology
D009243:NAD; D009536:Niacinamide; D009249:NADP; D009151:Mustard Gas