Development of Protective Agent Against Sulfur Mustard-Induced Skin Lesions
Abstract
The present study is a final report of the project. During the project we developed iodine formulation proved to be efficacious against SM in the guinea pig skin model at intervals of 15 and 30 rain between exposure and treatment. Incorporation of the antiinflammatory drug piroxicam and the steroidal antiinflamamtory agent clobetasol, caused the formulation to protect at intervals of 45 and 60 rain in the mouse ear swelling model and at 45 rain in the guinea pig skin irritation test. Introduction of ethanol to the formulation caused the preparation to be efficacious in the pig model; 20 rain interval between exposure and treatment caused significant protection. Longer intervals will be tested in the near future. The topical preparation was also effective against heat- and hydrofluoric acid-induced skin burns. Toxicokinetic studies with male, fur-covered and hairless guinea pigs showed that SM disappeared from the skin 60 rain after exposure whereas in the female, fur-covered guinea pig SM disappeared after 3 hours. Sodium hypochiorite inactivated SM in vitro but not in situ, namely, no significant inactivation by decontaminant applied on SM-exposed skin was observed. Iodine caused reduction in skin collagenase induced by mechlorethamine. COX2-deficient mice were less affected by SM that COX1-deficient end wild type mice. Iodine was also effective against dermally exposed organophosphate (paraoxon). The present study demonstrated that iodine induced skin protective peptides against noxious stimuli. Four peptides were identified and synthesized, of which two had protective activity when injected together with proteinase inhibitors to prevent degradation. Synthesis of N-methylated analogs produced metabolically stable peptides with protective activity against SM-induced skin lesions. Newly synthesized analogs showed protection in the mouse model when injected iv together with proinflammatory chemokine antibodies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA408037
Entities
People
- Uri Wormser
Organizations
- Hebrew University of Jerusalem