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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 (xmol 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 (xmol L~\ 30 (xmol L_1 or 60 (xmol 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.
KEYWORDS: CEES, cell viability, EB-1, EB-2, EB-3, EB-4, human epidermoid carcinoma cells, MTT test, organoselenium, pterostilbene, resveratrol, vesicant countermeasure
Sazetak
ANALOZI EPSELENA SMANJUJU TOKSICNOST 2-KLOROETIL ETILNOG SULFIDA U A-431- STANICAMA
Plikavci izazivaju izrazene mjehurice na kozi. Najpoznatiji je svakako sumporni iperit, koji se prvi put uporabio u 1. svjetskom ratu i do danasnjega daña nema djelotvornog protuotrova. U ispitivanju smo rabili zamjenu za iperit, 2-kloroetil etilni sulfid (CEES) da bismo testirali sposobnost resveratrola (RES) i pterostilbena (PTS), dvaju poznatih stilbenskih antioksidansa, organoselenijeva spoja epselena (EB-1) te njegovih triju analoga (EB-2, EB-3 i EB-4) da smanji toksicnost CEES-a u humanih stanica epidermoidnog karcinoma (A-431). Vijabilnost stanica testirali smo spomocu 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazol bromida (MTT) nakon 24-satne inkubacije s toksicnom koncentracijom CEES-a (1000 |¿mol L_1). Antioksidansi davani sami u razlicitim koncentracijama (15 (xmol L~\ 30 (xmol L~\ odnosno 60 (xmol L_1) nisu smanjili vijabilnost stanica. Dvadesetcetverosatna primjena CEES-a i testiranih antioksidansa pokazala je da samo EB-1 i njegovi analozi EB-2, EB-3 i EB-4 mogu sprijeciti smrt stanica, ali ne i stilbenski spojevi. EB-1 i EB-4 pokazali su se najdjelotvornijima u ublazavanju toksicnosti...