Brian Day, Ph.D.
University of Colorado, Denver
NIEHS Grant U54ES015678
A new study, funded in part by NIEHS, demonstrates the potential of an antioxidant metalloporphyrin in treating skin lesions caused by 2-chloroethyl ethyl sulfide (CEES), a chemical similar in structure to sulfur mustard gas that is used to study toxic effects of the chemical warfare agent. The findings show the antioxidant’s potential as a medical countermeasure against skin effects from exposure to chemical agents.
Since previous studies showed that oxidative stress plays a role in skin injuries caused by CEES, the researchers tested the ability of the antioxidant Mn(III) tetrakis(N,N'-diethylimidizolium-2-yl)porphyrin, known as AEOL 10150, to treat skin effects of CEES exposure. Mouse skin exposed to CEES and then treated with AEOL 10150 showed more than 50 percent (p < 0.05) reversal of increases in skin bi-fold and epidermal thickness and myeloperoxidase activity—all markers of CEES-induced skin injury—as well as decreased DNA oxidation.
Treating cultured mouse epidermal cells and human skin cells with AEOL 10150 (50 µM) 1 hour after CEES exposure brought about significant (p < 0.05) reversal of decreases in both cell viability and DNA synthesis induced by CEES. The researchers also measured reactive oxygen species in the cytoplasm and mitochondria, finding that the treatment improved CEES-induced oxidative stress in both cell lines.
Citation: Tewari-Singh N, Inturi S, Jain AK, Agarwal C, Orlicky DJ, White CW, Agarwal R, Day BJ. 2014. Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects. Free Radic Biol Med 72:285-95. (Brian Day is a consultant for and holds equity in Aeolus Pharmaceuticals, which is developing metalloporphyrins as potential therapeutic agents)