Treatment with the catalytic metalloporphyrin AEOL 10150 reduces inflammation and oxidative stress due to inhalation of the sulfur mustard analog 2-chloroethyl ethyl sulfide.
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.
Department of Pharmaceutical Sciences, University of Colorado at Denver Health Sciences Center, Denver, CO 80217, USA.
Heidi C
HC
O'Neill
Carl W
CW
White
Livia A
LA
Veress
Tara B
TB
Hendry-Hofer
Joan E
JE
Loader
Elysia
E
Min
Jie
J
Huang
Raymond C
RC
Rancourt
Brian J
BJ
Day
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D007249:Inflammation / Q000188:drug therapy; D019570:Inhalation Exposure; D007770:L-Lactate Dehydrogenase / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D009151:Mustard Gas / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
C472668:AEOL 10150; D000975:Antioxidants; D002619:Chemical Warfare Agents; D008665:Metalloporphyrins; C031278:2-chloroethyl ethyl sulfide; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D009151:Mustard Gas