Reduction of erythema in hairless guinea pigs after cutaneous sulfur mustard vapor exposure by pretreatment with niacinamide, promethazine and indomethacin.
Erythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD-induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin and promethazine used alone or in all possible combinations on the degree of erythema and histopathologic skin damage after HD exposure in HGP. Niacinamide (750 mg kg-1, i.p.), promethazine (12.5 mg kg-1, i.m.) or indomethacin (4 mg kg-1, p.o.) used singly or in combination was given as a 30-min pretreatment before an 8-min HD vapor cup skin exposure. Using a combination pretreatment of niacinamide, promethazine and indomethacin, erythema was reduced at 4 (91%) and 6 (55%) h, but not 24 h after HD. The incidence of histopathological skin changes (microvesicles, follicular involvement, epidermal necrosis, intracellular edema and pustular epidermatitis) 24 h after HD was not reduced. This study indicates that HD-induced erythema may result from several different mechanisms, including inflammation, histamine release and DNA damage. It is suggested that two phases of inflammation may occur: an early phase sensitive to antihistamines and non-steroidal antiinflammatory drugs and a late phase of extensive cell damage that was not sensitive to these drug pretreatments.
Yourick
J J
JJ
Applied Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425, USA.
Dawson
J S
JS
Mitcheltree
L W
LW
D000818:Animals; D001768:Blister / Q000139:chemically induced; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced; D004890:Erythema / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control; D006168:Guinea Pigs; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D009336:Necrosis; D009536:Niacinamide / Q000627:therapeutic use*; D011398:Promethazine / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000473:pathology
D009536:Niacinamide; D011398:Promethazine; D009151:Mustard Gas; D007213:Indomethacin