Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects.
Catalytic antioxidant AEOL 10150 treatment ameliorates sulfur mustard analog 2-chloroethyl ethyl sulfide-associated cutaneous toxic effects.
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DOI：
10.1016/j.freeradbiomed.2014.04.022
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发表时间：
2014-07
影响因子：
7.4
通讯作者：
Day, Brian J.
中科院分区：
文献类型：
--
作者：
Tewari-Singh, Neera;Inturi, Swetha;Jain, Anil K.;Agarwal, Chapla;Orlicky, David J.;White, Carl W.;Agarwal, Rajesh;Day, Brian J.
关键词：
Our previous studies and other published reports with the chemical warfare agent sulfur mustard (SM) and its analog 2-chloroethyl ethyl sulfide (CEES) have indicated a role of oxidative stress in skin injuries caused by these vesicating agents. We examined the effects of the catalytic antioxidant AEOL 10150 in attenuation of CEES-induced toxicity in our established skin injury models (skin epidermal cells and SKH-1 hairless mice) to validate the role of oxidative stress in the pathophysiology of mustard vesicating agents. Treatment of mouse epidermal JB6 and human HaCaT cells with AEOL 10150 (50 μM) 1 h post CEES exposure resulted in significant (p<0.05) reversal of CEES-induced decreases in both cell viability and DNA synthesis. Similarly, AEOL 10150 treatment 1 h after CEES exposure attenuated CEES-induced DNA damage in these cells. Similar AEOL 10150 treatments also caused significant (p<0.05) reversal of CEES-induced decreases in cell viability in normal human epidermal keratinocytes. Cytoplasmic and mitochondrial reactive oxygen species measurements showed that AEOL 10150 treatment drastically ameliorated the CEES-induced oxidative stress in both JB6 and HaCaT cells. Based on AEOL 10150 pharmacokinetic studies in SKH-1 mouse skin, mice were treated with topical formulation plus subcutaneous (injection; 5 mg/kg) AEOL 10150, 1 h after CEES (4 mg/mouse) exposure and every 4 h thereafter for 12 h. This AEOL 10150 treatment regimen resulted in over 50% (p<0.05) reversal in CEES-induced skin bi-fold and epidermal thickness, myeloperoxidase activity, and DNA oxidation in mouse skin. Results from this study demonstrate potential therapeutic efficacy of AEOL 10150 against CEES-mediated cutaneous lesions supporting AEOL 10150 as a medical countermeasure against SM-induced skin injuries.
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DOI：
10.1016/0272-0590(85)90123-x
发表时间：
1985-12-01
期刊：
FUNDAMENTAL AND APPLIED TOXICOLOGY
影响因子：
--
作者：
PAPIRMEISTER, B;GROSS, CL;JOHNSON, JB
通讯作者：
JOHNSON, JB
影响因子：
3.9
作者：
Day, BJ;Fridovich, I;Crapo, JD
通讯作者：
Crapo, JD
影响因子：
7.4
作者：
Day, BJ;Batinic-Haberle, I;Crapo, JD
通讯作者：
Crapo, JD
DOI：
10.1124/jpet.108.145037
发表时间：
2009-03-01
影响因子：
3.5
作者：
Gould, Neal S.;White, Carl W.;Day, Brian J.
通讯作者：
Day, Brian J.
影响因子：
5.8
作者：
Kachadourian, R;Johnson, CA;Day, BJ
通讯作者：
Day, BJ