title: Ebselen analogues reduce 2-chloroethyl ethyl sulphide toxicity in A-431 cells.
abstract: Vesicants are potent blistering agents. The prototype vesicant is sulphur mustard gas, first used in World War I, which still has no effective antidote. We used a mustard gas surrogate 2-chloroethyl ethyl sulphide (CEES) to study the ability of resveratrol (RES) and pterostilbene (PTS), two well-established stilbene antioxidants, ebselen (EB-1), an organoselenium compound, and three EB-1 analogues (EB-2, EB-3, and EB-4) to reduce CEES toxicity in human epidermoid carcinoma cells (A-431). Following a 24-hour incubation of a toxic concentration of CEES (1000 μmol L-1), we used the MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide] test to analyse cell viability. Different concentrations of test antioxidants alone (15 μmol L-1, 30 μmol L-1 or 60 μmol L-1) did not decrease cell viability. Treatment with CEES and test antioxidants for 24 h showed that only EB-1 and its analogues EB-2, EB-3, and EB-4 but not the stilbene compounds could rescue the cells from death. EB-1 and EB-4 were the most effective at reducing CEES cytotoxicity and did so in a concentration-dependent manner, while EB-2 and EB-3 demonstrated the least protective effect. In summary, the data described herein indicate that organoselenium antioxidants, especially EB-4, may prove useful as countermeasures to blistering agents.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Jamaica, NY 11439, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pino
authors.forename: Magdalena
authors.initials: M
authors.lastname: Pietka-Ottlik
authors.forename: Blase
authors.initials: B
authors.lastname: Billack
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D006801:Humans; D054833:Isoindoles; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000633:toxicity; D016566:Organoselenium Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001393:Azoles; D002619:Chemical Warfare Agents; D054833:Isoindoles; D016566:Organoselenium Compounds; D020011:Protective Agents; D013267:Stilbenes; C107773:pterostilbene; C042986:ebselen; C031278:2-chloroethyl ethyl sulfide; D000077185:Resveratrol; D009151:Mustard Gas