Effectiveness of Cytoprotective Agents on Sulfur Mustard Induced Toxicity: The In vitro Model

Abstract

Sulphur mustard (bis (2-chloroethyl) sulfide, SM) is a powerful vesicating chemical warfare agent that causes profound injuries to the eyes, lungs and skin. Despite intensive research following the first use of SM in World War I, there is still no useful pretreatment or therapeutic antidote available. This agent remains a constant chemical threat. A potential approach to combating the debiliting effects of this agent is the use of compounds that can react with this material before it interacts with critical macromolecules. Glutathione (GSH), a tripeptide that exists in high concentrations in cells, reacts with SM and is involved in SM detoxification. Amifostine is a synthetic aminothiol, has been extensively used as a radioprotector. This prompted us to evaluate the protective efficacy of GSH, Amifostine and DRDE-07 (S-2(2- aminoethyl amino) ethyl phenyl sulfide) (synthesized in our lab) against SM toxicity in vitro in HeLa cell line. All these compounds are thiol group containing compounds. Pretreatment of HeLa cell with these cytoprotectants led to decrease in cytotoxicity after SM exposure. The protective efficacy of above compounds were evaluated against sulphur mustard using HeLa cells. The above compounds were added to the media 1 hr before the SM exposure and incubated for 24 hrs. cell viability by MTT assay and LDH leakage were measured as end point.