Document Detail

Evaluation of protective effects of sodium thiosulfate, cysteine, niacinamide and indomethacin on sulfur mustard-treated isolated perfused porcine skin.
MedLine Citation:
PMID:  7750164     Owner:  NLM     Status:  MEDLINE    
Sulfur mustard (bis(2-chloroethyl)sulfide, HD), a bifunctional alkylating agent, causes severe cutaneous injury, including cell death, edema and vesication. However, the mechanisms underlying HD-induced cutaneous toxicity remain undefined. The isolated perfused porcine skin flap (IPPSF) has been utilized to investigate dermal toxic compounds and pharmacological intervention. In this study, 4 compounds with different pharmacological mechanisms were tested for their ability to prevent the dark basal cell formation, vesication and vascular response charcteristic of exposure to HD in the IPPSF. Reduction of HD-induced dark basal cells was observed in IPPSFs perfused with sodium thiosulfate and cysteine, which are HD scavengers; niacinamide, a possible NAD+ stabilizer and an inhibitor of poly (ADP-ribose) polymerase; or indomethacin, a cyclooxygenase inhibitor, respectively. Treatments with niacinamide and indomethacin, but not sodium thiosulfate or cysteine, resulted in an inhibition of the vascular response in IPPSF exposed to HD. Microvesicles caused by HD were only partially prevented in the indomethacin-perfused IPPSFs. These data suggest that none of these agents alone would be successful antivesicant agents and different mechanisms are involved in production of HD-induced dark basal cells, microvesicles and the vascular response; unfortunately, blocking of the cellular toxicity as evidenced by dark basal cell formation did not prevent vesication, suggesting that other mechanisms must be operative and that there is a multistep, biochemical process that leads to a final lesion.
Z Zhang; J E Riviere; N A Monteiro-Riviere
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  96     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-06-22     Completed Date:  1995-06-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  249-62     Citation Subset:  IM    
Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606, USA.
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MeSH Terms
Cysteine / pharmacology*
Dinoprostone / metabolism
Indomethacin / pharmacology*
Mustard Gas* / toxicity
Niacinamide / pharmacology*
Skin / blood supply
Skin Diseases / chemically induced*,  pathology
Thiosulfates / pharmacology*
Reg. No./Substance:
0/Thiosulfates; 363-24-6/Dinoprostone; 505-60-2/Mustard Gas; 52-90-4/Cysteine; 53-86-1/Indomethacin; 7772-98-7/sodium thiosulfate; 98-92-0/Niacinamide

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