The use of doxycycline as a protectant against sulphur mustard in HaCaT cells.
As part of an ongoing programme on medical countermeasures against the chemical warfare agent sulphur mustard (HD) and set against the background of the involvement of matrix metalloproteinases (MMPs) in the pathology of HD-induced vesication processes, the potentially beneficial effects of doxycycline on cell attachment was determined in confluent HaCaT cell cultures exposed to HD. Doxycycline was found to inhibit to a significant extent the tendency of HD-exposed cells to detach from the growth substrate, however, analysis of the metabolic activity of the adherent cells indicated that doxycycline treatment did not maintain cell viability. It was confirmed that apoptosis was the predominant mode of HD-induced cell death. The results suggested that doxycycline and other MMP inhibitors may have a role to play in therapeutic intervention against HD exposure, but only as part of a combination therapy. The specific value of protease inhibitors in this capacity remains to be determined.
Lindsay
Christopher D
CD
Biomedical Sciences Department, Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. cdlindsay@dstl.gov.uk
Gentilhomme
Edgar
E
Mathieu
Jacques D
JD
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004396:Coloring Agents; D004318:Doxycycline / Q000494:pharmacology*; D005434:Flow Cytometry; D005840:Gentian Violet; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008858:Microscopy, Phase-Contrast; D009151:Mustard Gas / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000900:Anti-Bacterial Agents; D002619:Chemical Warfare Agents; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D005840:Gentian Violet; D004318:Doxycycline; D009151:Mustard Gas