Effects of Lewisite on cell membrane integrity and energy metabolism in human keratinocytes and SCL II cells

Lewisite is a highly toxic arsenic compound which can cause skin damage. In the present study effects of Lewisite on cell membrane integrity and energ y metabolism as well as antidotal effects of DL-2,3-dimercaptopropanesulfon ate (DMPS). and meso-2,3-dimercaprosuccinic acid (m-DMSA) were investigated in a keratinocyte derived cell line (SCL II) and primary human keratinocyt es (HK). Cells were incubated in Lewisite (60 muM) containing medium for 5 min. During the following 6 h lactate dehydrogenase (LDH) activity in the s upernatant. intracellular ATP content. tetrazolium reduction. glucose consu mption and lactate formation were measured. Glucose consumption and lactate production were decreased in both cell lines after Lewisite exposure. In S CL II cells an increase of LDH activity in the supernatant, a decrease of A TP content. and an impaired ability to reduce tetrazolium was found 3 h aft er Lewisite exposure. In HK cultures tetrazolium reduction was significantl y decreased already after 2 hi whereas LDH increase in the supernatant and ATP content decrease occurred only at 6 h after Lewisite exposure. When DMP S or m-DMSA was added directly after Lewisite exposure to SCL II cells, glu cose consumption and lactate formation were restored and LDH leakage was pr evented. SCL II cells might be more prone to membrane damage whereas in ker atinocytes mitochondrial impairment seems to be the predominant effect of L ewisite. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.