The use of doxycycline as a protectant against sulphur mustard in HaCaT cells

Abstract

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.

Extracellular epimorphin impairs expression and processing of profilaggrin in HaCaT keratinocytes

“…2C). It is notable, however, that doxycycline reportedly exerts unexpected functions in addition to antibacterial actions in keratinocytes [31][32][33][34]. To further ascertain the effect of extracellular EPM on the attenuation of Pro-FLG, parental HaCaT cells were treated with active form of recombinant EPM (r-EPM), in the absence of dox.…”

Dermal Toxicity of Sulfur Mustard

“…Explant cultures of SM-treated human skin co-treated with Ilomastat showed no epidermal-dermal separation (Schultz et al, 2004). However, doxycycline does not protect HaCaT viability; cells lose adherence and undergo apoptosis (Lindsay et al, 2007). The antibiotic doxycycline is also an MMP inhibitor that was shown to attenuate SM-induced pulmonary and ocular injury (Guignabert et al, 2005;Horwitz et al, 2014).…”

Flavonoid Treatment for Mustard Agents' Toxicity

“…Doxycycline may be a promising therapeutic agent for SM (Guignabert et al, 2005). For the lung lesions and systemic toxicity of SM, paracetamol-ibuprofen combination for controlling pain and fever, beclomethasone inhaler as an anti-inflammatory corticosteroid, codeine phosphate or sulphate as a cough suppressant, doxycycline as an antibacterial agent, and N-acetyl cysteine, as a mucolytic and glutathione sparing drug are recommended (Lindsay et al, 2008, Bobb et al, 2005Ghanei et al, 2007, Vijayaraghavan et al, 2011. If haemoconcentration and shock are present either whole blood transfusion or transfusion of plasma expanders should be considered.…”