Riviere, J.E., N.A. Monteiro-Riviere and A.O. Inman. The Effect of Altered Media Flow and Glucose Concentration on Sulfur Mustard Toxicity in the Isolated Perfused Porcine Skin Flap. In Vitro Toxicol. 1997. 10(2): 169-181.

sulfur mustard - 00505-60-2

The isolated perfused porcine skin flap (IPPSF), a novel alternative in vitro cutaneous model, has proven useful in the study of the pathogenesis of sulfur mustard (HD)-induced toxicity. The IPPSF is normally perfused at a media flow rate of 1.5 mL/min and glucose concentration of 120 mg/dL. This study assessed the effects of altered flow (0.5 or 3.0 mL/min) and glucose (50 or 400 mg/dL) on pathogenesis after ethanol control (EtOH) and HD (10.0 mg/mL) dosing. Pathogenesis in the flap was assessed by biochemical cumulative glucose utilization (CGU), physiological (vascular resistance), and morphological (light microscopy and transmission electron microscopy) endpoints. Vesication secondary to HD treatment was always associated with the formation of dark basal cells. The vascular resistance (VR) of HD-treated flaps increased while the CGU decreased with a decrease in media flow. High flow caused an increase in cytotoxicity in the control flaps evidenced by severe intracellular epidermal edema, paranuclear vacuoles, and epidermal-dermal separation. The VR was highest in the EtOH-treated low glucose flaps and the lowest in the HD-treated high glucose flaps. The CGU was directly proportional to the glucose concentration. While low concentrations of glucose resulted in blister formation and severe cellular cytotoxicity in the EtOH controls, high glucose blocked the formation of microvesicles and blisters in HD-treated IPPSFs despite moderate cytotoxicity. In summary, increased availability of glucose to the IPPSF modulates HD-induced cytotoxicity.