Sulfur mustard (bis-2-(chloroethyl)
sulfide; SM) is a highly reactive vesicating and alkylating
chemical warfare agent. A SM analog,
2-chloroethyl ethyl sulfide (
CEES), has been utilized to elucidate mechanisms of toxicity and as a screen for
therapeutics. Previous studies with SM and
CEES have demonstrated a role for oxidative stress as well as decreased injury with
antioxidant treatment. We tested whether posttreatment with the
metalloporphyrin catalytic
antioxidant AEOL 10150 would improve outcome in
CEES-induced
lung injury. Anesthetized rats inhaled 5%
CEES for 15 min via a nose-only inhalation system. At 1 and 9 h after
CEES exposure, rats were given
AEOL 10150 (5 mg/kg, sc). At 18 h post-
CEES exposure BALF
lactate dehydrogenase activity,
protein,
IgM, red blood cells, and neutrophils were elevated but were decreased by
AEOL 10150 treatment. Lung
myeloperoxidase activity was increased after
CEES inhalation and was ameliorated by
AEOL 10150. The lung oxidative stress markers 8-OHdG and 4-HNE were elevated after
CEES exposure and significantly decreased by
AEOL 10150 treatment. These findings demonstrate that
CEES inhalation increased
lung injury,
inflammation, and oxidative stress, and
AEOL 10150 was an effective rescue agent. Further investigation utilizing catalytic
antioxidants as treatment for SM inhalation injury is warranted.