Sulfur mustard (bis 2-chloroethyl ethyl
sulfide, SM) is a powerful bi-functional vesicating
chemical warfare agent. SM tissue injury is partially mediated by the overproduction of
reactive oxygen species resulting in oxidative stress. We hypothesized that using a catalytic
antioxidant (
AEOL 10150) to alleviate oxidative stress and secondary
inflammation following exposure to SM would attenuate the toxic effects of SM inhalation. Adult male rats were intubated and exposed to SM (1.4 mg/kg), a dose that produces an LD50 at approximately 24 h. Rats were randomized and treated via
subcutaneous injection with either sterile PBS or
AEOL 10150 (5 mg/kg, sc, every 4 h) beginning 1 h post-SM exposure. Rats were euthanized between 6 and 48 h after exposure to SM and survival and markers of injury were determined. Catalytic
antioxidant treatment improved survival after SM inhalation in a dose-dependent manner, up to 52% over SM PBS at 48 h post-exposure. This improvement was sustained for at least 72 h after SM exposure when treatments were stopped after 48 h. Non-invasive monitoring throughout the duration of the studies also revealed blood
oxygen saturations were improved by 10% and clinical scores were reduced by 57% after SM exposure in the catalytic
antioxidant treatment group. Tissue analysis showed catalytic
antioxidant therapy was able to decrease airway cast formation by 69% at 48 h post-exposure. To investigate
antioxidant induced changes at the peak of injury, several
biomarkers of oxidative stress and
inflammation were evaluated at 24 h post-exposure.
AEOL 10150 attenuated SM-mediated lung
lipid oxidation, nitrosative stress and many proinflammatory
cytokines. The findings indicate that catalytic
antioxidants may be useful medical countermeasure against inhaled SM exposure.