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 μM) protected skin cells from the toxicity of both HN2 (10–80 μM) and CEES (10–40 μM), BHA (100 μM) 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.

Keywords:

• Butylated hydroxyanisole
• Ebselen
• Mechlorethamine
• 2-chloroethylethyl sulfide
• A-431
• Vesicant

Acknowledgments

This work was funded by the Department of Pharmaceutical Sciences (St. John's University). The authors are also extremely grateful to Dr. Cesar Lau-Cam and Dr. Diane Hardej (St. John's University) for interesting discussions pertaining to this work.