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Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously Exposed to Sulfur Mustard

Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously... Abstract Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously Exposed to Sulfur Mustard. YOURICK, J. J., CLARK, C. R., AND MITCHELTREE. L. W. (1991). Fundam. Appl. Toxicol., 17, 533–;542. 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-mm pretreatment inhibited microvesicle formation by 50% after HD application. However, niacinamide given 2 hr after RD 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. This content is only available as a PDF. Author notes 1 In conducting the research described in this report, the investigators adhered to the “Guide for the Care and Use of Laboratory Animals”, NIH Publication No. 85–23, revised 1985. 2 Disclaimer Note: The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense. © 1991 by the Society of Toxicology http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Toxicological Sciences Oxford University Press

Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously Exposed to Sulfur Mustard

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Publisher
Oxford University Press
Copyright
© 1991 by the Society of Toxicology
ISSN
1096-6080
eISSN
1096-0929
DOI
10.1093/toxsci/17.3.533
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Abstract

Abstract Niacinamide Pretreatment Reduces Microvesicle Formation in Hairless Guinea Pigs Cutaneously Exposed to Sulfur Mustard. YOURICK, J. J., CLARK, C. R., AND MITCHELTREE. L. W. (1991). Fundam. Appl. Toxicol., 17, 533–;542. 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-mm pretreatment inhibited microvesicle formation by 50% after HD application. However, niacinamide given 2 hr after RD 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. This content is only available as a PDF. Author notes 1 In conducting the research described in this report, the investigators adhered to the “Guide for the Care and Use of Laboratory Animals”, NIH Publication No. 85–23, revised 1985. 2 Disclaimer Note: The opinions or assertions contained herein are the private views of the authors and are not to be construed as reflecting the views of the Department of the Army or the Department of Defense. © 1991 by the Society of Toxicology

Journal

Toxicological Sciences – Oxford University Press

Published: Oct 1, 1991

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