Attenuation of sulfur mustard toxicity by S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) in mouse liver

Abstract

Sulfur mustard (SM) (bis-(2-chloroethyl) sulfide) is a chemical warfare agent. Evaluation of toxicity and protective effect of DRDE-07 (S-2(2-aminoethylamino)ethyl phenyl sulfide) was studied in mouse liver after SM challenging. Female mice were given orally 0.2 LD₅₀ of DRDE-07 (249 mg/kg body weight) and exposed percutaneously with 1.0 LD₅₀ of SM (8.1 mg/kg body weight). Gene expression profiles were determined using global genome microarray analysis at 3 days post-exposure. DRDE-07 alone treated animal showed significant upregulation to metabolism of xenobiotics by cytochrome P450 pathways. Genes related to cell adhesion molecules (CAMs), were downregulated. DRDE-07 pretreated SM exposed animals showed upregulation of xenobiotic cytochrome P450 pathway genes. Antigen presenting, cell adhesion molecules, cytokine, cytokine receptor metabolism, fatty acid metabolism, glutathione metabolism, cell cycle signaling pathway genes showed downregulation. The present study showed that SM-induced toxicity in mouse liver was attenuated by the pretreatment with DRDE-07.

Keywords::

• Sulfur mustard
• DRDE-07
• microarray analysis
• gene expression
• semi-quantitative PCR