Zhang, Z., J. E. Riviere, and N.A. Monteiro-Riviere. Protective Effects of Sodium Thiosulfate, Cysteine, Niacinamide, and Indomethacin on Sulfur Mustard-Treated Isolated Perfused Porcine Skin. The Toxicologist 1996. 30: 171.

sulfur mustard - 00505-60-2

Sulfur mustard (HD), a bifunctional alkylating agent, causes dark basal cells (DBCs), vesication, and an increase in vascular resistance (VR). The isolated perfused porcine skin flap (IPPSF) was used to test the efficacy of pharmacological intervention of 4 compounds on HD dermal toxicity. IPPSFs were infused with 10-3 M of sodium thiosulfate, 10-2 M of cysteine, 10-3 M niacinamide, or 2x10-4 M of indomethacin for 2 hrs, treated with 5.0 mg/ml HD, then perfused for an additional 6 hrs. Mean DBCs for HD alone were 19.7%, but decrease to 3.9% sodium thiosulfate, 4.2% cysteine, 5.8% niacinamide, or 1.0% indomethacin. Niacinamide and indomethacin caused a decrease in VR, while only indomethacin partially prevented microvesicles. These compounds alone would not be efficacious antivesicant agents. Blocking of DBCs did not prevent vesication, indicating that different mechanisms are involved in HD-induced DBCs, microvesicles, and VR. Therefore, there is a multistep, biochemical process which finally culminates in blister formation.