title: Protective effect of liposome-encapsulated glutathione in a human epidermal model exposed to a mustard gas analog.
abstract: Sulfur mustard or mustard gas (HD) and its monofunctional analog, 2-chloroethyl ethyl sulfide (CEES), or "half-mustard gas," are alkylating agents that induce DNA damage, oxidative stress, and inflammation. HD/CEES are rapidly absorbed in the skin causing extensive injury. We hypothesize that antioxidant liposomes that deliver both water-soluble and lipid-soluble antioxidants protect skin cells from immediate CEES-induced damage via attenuating oxidative stress. Liposomes containing water-soluble antioxidants and/or lipid-soluble antioxidants were evaluated using in vitro model systems. Initially, we found that liposomes containing encapsulated glutathione (GSH-liposomes) increased cell viability and attenuated production of reactive oxygen species (ROS) in HaCaT cells exposed to CEES. Next, GSH-liposomes were tested in a human epidermal model, EpiDerm. In the EpiDerm, GSH-liposomes administered simultaneously or 1 hour after CEES exposure (2.5 mM) increased cell viability, inhibited CEES-induced loss of ATP and attenuated changes in cellular morphology, but did not reduce caspase-3 activity. These findings paralleled the previously described in vivo protective effect of antioxidant liposomes in the rat lung and established the effectiveness of GSH-liposomes in a human epidermal model. This study provides a rationale for use of antioxidant liposomes against HD toxicity in the skin considering further verification in animal models exposed to HD.
authors.affiliation: Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Paromov
authors.forename: Sudha
authors.initials: S
authors.lastname: Kumari
authors.forename: Marianne
authors.initials: M
authors.lastname: Brannon
authors.forename: Naga S
authors.initials: NS
authors.lastname: Kanaparthy
authors.forename: Hongsong
authors.initials: H
authors.lastname: Yang
authors.forename: Milton G
authors.initials: MG
authors.lastname: Smith
authors.forename: William L
authors.initials: WL
authors.lastname: Stone