title: Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis.
abstract: A series of test compounds were evaluated for an ability to reduce the toxicity of the nitrogen mustard mechlorethamine (HN2) in vitro. The test compounds included resveratrol, pterostilbene, vitamin C, ebselen, ebselen diselenide, and ebselen-sulfur. Among them, ebselen demonstrated the highest degree of protection against HN2 toxicity. To this end, pretreatment of the cells with ebselen offered protection against the toxicant whereas no protection was observed when cells were first incubated with HN2 and then treated with ebselen. Significant increases in caspase 3 and caspase 9 activities were observed in response to HN2, and ebselen was found to reduce these effects. Taken together, the data presented here indicate that ebselen is an effective countermeasure to nitrogen mustard in vitro, which is worthy of future investigation in vivo.
authors: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA.
authors: Anju
authors: A
authors: Lulla
authors: Maria A
authors: MA
authors: Pino
authors: Magdalena
authors: M
authors: Piętka-Ottlik
authors: Jacek
authors: J
authors: Młochowski
authors: Oleksiy
authors: O
authors: Sparavalo
authors: Blase
authors: B
authors: Billack
mesh_terms: D000931:Antidotes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D001393:Azoles / Q000008:administration & dosage / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002619:Chemical Warfare Agents / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D007509:Irritants / Q000037:antagonists & inhibitors / Q000633:toxicity; D054833:Isoindoles; D008466:Mechlorethamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000931:Antidotes; D000975:Antioxidants; D001393:Azoles; D002619:Chemical Warfare Agents; D007509:Irritants; D054833:Isoindoles; D016566:Organoselenium Compounds; D013267:Stilbenes; C107773:pterostilbene; C042986:ebselen; D008466:Mechlorethamine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D001205:Ascorbic Acid; D000077185:Resveratrol