title: Reduction of vesicant toxicity by butylated hydroxyanisole in A-431 skin cells.
abstract: Mechlorethamine (HN2) and 2-chloroethylethyl sulfide (CEES) are mustard vesicants. Butylated hydroxyanisole (BHA) is a phenolic antioxidant. In the present work, the ability of BHA to reduce the toxicity of HN2 and CEES was investigated using A-431 skin cells. HN2 toxicity was found to be dependent, at least in part, on the cellular glutathione (GSH) status. BHA also decreased HN2-induced DNA damage and lipid peroxidation. The cytoprotective activity of BHA was also compared with that of the structurally unrelated antioxidant ebselen. Whereas ebselen (30 microM) protected skin cells from the toxicity of both HN2 (10-80 microM) and CEES (10-40 microM), BHA (100 microM) reduced the toxicity of HN2 only. Taken together, these data suggest that antioxidants such as BHA or ebselen may serve as useful treatments for injury caused by blistering agents.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Jamaica, New York, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pino
authors.forename: Blase
authors.initials: B
authors.lastname: Billack
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000633:toxicity; D002083:Butylated Hydroxyanisole / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002619:Chemical Warfare Agents / Q000633:toxicity*; D053938:DNA Fragmentation / Q000187:drug effects; D000078404:Epidermal Cells; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D054833:Isoindoles; D008466:Mechlorethamine / Q000737:chemistry / Q000633:toxicity*; D015394:Molecular Structure; D009151:Mustard Gas / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D016566:Organoselenium Compounds / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D001393:Azoles; D002619:Chemical Warfare Agents; D054833:Isoindoles; D016566:Organoselenium Compounds; D002083:Butylated Hydroxyanisole; C042986:ebselen; D019328:Buthionine Sulfoximine; D008466:Mechlorethamine; C031278:2-chloroethyl ethyl sulfide; D005978:Glutathione; D009151:Mustard Gas