Analozi epselena smanjuju toksičnost 2-kloroetil etilnog sulfida u A-431-stanicama

• Main Authors: Pino, Maria A.; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Jamaica, NY USA, Pietka-Ottlik, Magdalena; Division of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland, Billack, Blase; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, Jamaica, NY USA; [e-mail]
• Format: Text
• Language: English
• Published: Institute for Medical Research and Occupational Health 2013
• Subjects: CEES; EB-1; EB-2; EB-3; EB-4; humane stanice epidermoidnog karcinoma; MTTtest; organoselenij; plikavci; protuotrov; pterostilben; resveratrol; vijabilnost stanica; cell viability; human epidermoid carcinoma cells; MTT test; organoselenium; pterostilbene; vesicant countermeasure; sami
• Online Access: http://hrcak.srce.hr/98685; http://hrcak.srce.hr/file/145310

Plikavci izazivaju izražene mjehuriće na koži. Najpoznatiji je svakako sumporni iperit, koji se prvi put uporabio u 1. svjetskom ratu i do današnjega dana nema djelotvornog protuotrova. U ispitivanju smo rabili zamjenu za iperit, 2-kloroetil etilni sulfi d (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 toksičnost CEES-a u humanih stanica epidermoidnog karcinoma (A-431). Vijabilnost stanica testirali smo s pomoću 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazol bromida (MTT) nakon 24-satne inkubacije s toksičnom koncentracijom CEES-a (1000 μmol L-1). Antioksidansi davani sami u različitim koncentracijama (15 μmol L-1, 30 μmol L-1, odnosno 60 μmol L-1) nisu smanjili vijabilnost stanica. Dvadesetčetverosatna primjena CEES-a i testiranih antioksidansa pokazala je da samo EB-1 i njegovi analozi EB-2, EB-3 i EB-4 mogu spriječiti smrt stanica, ali ne i stilbenski spojevi. EB-1 i EB-4 pokazali su se najdjelotvornijima u ublažavanju toksičnosti CEES-a u skladu s koncentracijom, dok su se EB-2 i EB-3 pokazali najmanje djelotvornima. Ovdje prikazani podaci upućuju na to da organoselenijevi antioksidansi, a napose EB-4, mogu biti korisni protuotrovi plikavcima. 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.