Investigating the Role of Sulfur Mustard in Triggering Molecular Inflammatory Mechanisms

Abstract

Sulfur mustard, a chemical warfare agent, that has been used in the Iraq-Iran conflict, exerts its devastating effects through multifaceted biochemical pathways. Its primary mode of action involves the alkylation of cellular macromolecules, particularly DNA and proteins, leading to cellular dysfunction and damage. DNA alkylation by sulfur mustard results in the formation of adducts, causing genetic mutations, chromosomal aberrations and ultimately cell death or malignant transformation. Similarly, protein alkylation disrupts cellular signaling pathways and homeostasis, contributing to tissue damage and dysfunction. Additionally, sulfur mustard exposure induces the generation of reactive oxygen species, exacerbating cellular damage, inflammation, and oxidative stress. This triggers the activation of inflammatory pathways, including NF-κB, MAPK, JAK/STAT and inflammasome activation, leading to the production of cytokines, adhesion molecules, chemokines, activator protein-1 (AP-1), and other inflammatory mediators. The inflammatory cascade initiated by sulfur mustard exposure perpetuates tissue damage, immune cell recruitment and systemic effects, enhancing acute symptoms and potential long-term health complications.