Sulfur mustard toxicity: History, chemistry, pharmacokinetics, and pharmacodynamics

Abstract

Sulfur mustard (SM) and similar bifunctional agents have been used as chemical weapons for almost 100 years. Victims of high-dose exposure, both combatants and civilians, may die within hours or weeks, but low-dose exposure causes both acute injury to the eyes, skin, respiratory tract and other parts of the body, and chronic sequelae in these organs are often debilitating and have a serious impact on quality of life. Ever since they were first used in warfare in 1917, SM and other mustard agents have been the subjects of intensive research, and their chemistry, pharmacokinetics and mechanisms of toxic action are now fairly well understood. In the present article we review this knowledge and relate the molecular-biological basis of SM toxicity, as far as it has been elucidated, to the pathological effects on exposure victims.

A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications

“…A growing body of evidence has confirmed the pivotal role of inflammation in the ethiopathogenesis of both acute and chronic SM toxicity. 3,4 SM has been shown to up-regulate the expression of several proinflammatory mediators in keratinocytes, including IL-6, IL-8, tumor necrosis factor-a and CGRP. Such an inflammatogenic effect of SM is, at least in part, due to the activation of proinflammatory factors such as nuclear factor (NF)-kB, mitogenactivated protein kinases and activator protein-1.…”

“…2 Although the pathophysiology of SM toxicity has not been fully clarified, DNA damage and resulting inflammatory and oxidative responses are considered as cornerstones of pathological effects. 3,4 Along with lungs and eyes, skin is among the most sensitive organs to SM that could undergo several types of damage based on the SM dose and duration of exposure. 3,5 Cutaneous complications of SM have been chronologically classified into acute and chronic.…”

Sulfur mustard and respiratory diseases: Revisit with special reference to the “Comments on ‘Sulfur Mustard and Respiratory Diseases’, Tang and Loke () and a prepared Integrated Mechanism for Chronic Pulmonary Disease from Exposure to Sulfur Mustard” by Saburi and Ghanei ()

“…In Figure 1 from the letter, Saburi and Ghanel described the mechanisms of chronic pulmonary consequences of HD exposure based on their previous research on victims 15 years after exposure to HD (Ghabili et al, 2011;. However, data indicated from the authors' research are insufficient to draw this mechanistic figure.…”

Comments on “Sulfur Mustard and Respiratory Diseases,” Tang & Loke (2012) and a prepared integrated mechanism for chronic pulmonary disease from exposure to sulfur mustard

“…(6) Finally, although they skillfully gathered and assessed the findings about chronic pulmonary effect of SM, they did not interpret the findings in an integrated manner. Figure 1 shows the approach to describing the mechanisms of chronic pulmonary consequences of SM exposure based on our previous research (Ghabili et al, 2011;Ghanei & Harandi 2007. (7) In addition, it seems that metabolomics and proteomic studies cannot justify all aspects of pulmonary involvements in these cases and a comprehensive genomic study focusing on the target points of human genomes (such as a probable mutation in any segment of DNA which may have a significant role in repair) is mandatory.…”