title: Niacinamide pretreatment reduces microvesicle formation in hairless guinea pigs cutaneously exposed to sulfur mustard.
abstract: It has been proposed that sulfur mustard (HD) may indirectly activate poly(ADP-ribose) polymerase (PADPRP) by alkylating cellular DNA (Papirmeister et al., 1985). Activation of PADPRP results in the depletion of cellular NAD+, which initiates a series of biochemical processes that have been proposed to culminate in blister formation. Preventing PADPRP activation and NAD+ depletion should inhibit blister formation. Niacinamide is both an inhibitor of PADPRP and a precursor for NAD+ synthesis. The present study was undertaken to determine whether niacinamide can protect against HD-induced microvesication in cutaneously exposed hairless guinea pigs. Each site was exposed to HD for 8 min by means of a vapor cup. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment inhibited microvesicle formation by 50% after HD application. However, niacinamide given 2 hr after HD application did not reduce microvesicle formation. There was no benefit when niacinamide was given as both a pretreatment and treatment when compared to niacinamide given only as a pretreatment. The reduction in microvesication 24 hr after HD did not correlate with skin NAD+ content. Niacinamide did not reduce the degree of erythema or edema. Ballooning degeneration of basal epidermal cells was present in some niacinamide pretreated HD exposure sites. These results suggest that niacinamide may only be effective as a pretreatment compound to reduce the incidence of HD-induced microvesicle formation. Maintenance of skin NAD+ content may not be solely responsible for inhibiting microvesicle formation and inhibition of PADPRP may be of greater importance.
authors.affiliation: Applied Pharmacology Branch, United States Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yourick
authors.forename: C R
authors.initials: CR
authors.lastname: Clark
authors.forename: L W
authors.initials: LW
authors.lastname: Mitcheltree
mesh_terms: D000818:Animals; D001706:Biopsy; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced; D006168:Guinea Pigs; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000473:pathology
chemical_list: D009243:NAD; D009536:Niacinamide; D009151:Mustard Gas