Sulfur mustard-induced microvesication in hairless guinea pigs: effect of short-term niacinamide administration.
It has been postulated that sulfur mustard (HD) damage may activate poly(ADP-ribose) polymerase (PADPRP), resulting in depletion of cellular NAD+. This biochemical alteration is postulated to result in blister (vesicle) formation. It has been previously demonstrated that niacinamide (NAM), an inhibitor of PADPRP and a precursor for NAD+ synthesis, may be useful as a pretreatment compound to reduce HD-induced microvesication. The present study was undertaken to determine whether niacinamide's protective action could be extended beyond 24 hr and if the degree of microvesication is related to changes in skin NAD+ content. HD exposures were made by vapor cup to hairless guinea pigs. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment did not reduce the degree of microvesication 72 hr after HD compared to saline controls. However, niacinamide given as a 30-min pretreatment and at 6-, 24-, and 48-hr after HD, exhibited a 28% reduction in microvesication 72 hr after HD. Skin NAD+ content at 72 hr after HD was depleted by approximately 53% in the saline and NAM-treated groups. Skin NAD+ content was depleted despite NAM administration. Niacinamide did not reduce the degree of erythema at 48 or 72 hr. These results suggest that niacinamide's protective effect against HD-induced microvesication may be extended for at least 72 hr, but NAM levels must be sustained during the post-HD period. The link between maintenance of skin NAD+ and reductions in microvesication is still uncertain.
Yourick
J J
JJ
Applied Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
Dawson
J S
JS
Mitcheltree
L W
LW
D000818:Animals; D001768:Blister / Q000139:chemically induced / Q000517:prevention & control*; D004789:Enzyme Activation / Q000187:drug effects; D004890:Erythema / Q000139:chemically induced / Q000188:drug therapy; D006168:Guinea Pigs; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D009536:Niacinamide; D011065:Poly(ADP-ribose) Polymerases; D009151:Mustard Gas