Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog
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 antiox...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Journal of Toxicology |
| Online Access: | http://dx.doi.org/10.1155/2011/109516 |
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| author | Victor Paromov Sudha Kumari Marianne Brannon Naga S. Kanaparthy Hongsong Yang Milton G. Smith William L. Stone |
| author_facet | Victor Paromov Sudha Kumari Marianne Brannon Naga S. Kanaparthy Hongsong Yang Milton G. Smith William L. Stone |
| author_sort | Victor Paromov |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-339bf1496784486aa23854c037f6f16e |
| institution | Kabale University |
| issn | 1687-8191 1687-8205 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Toxicology |
| spelling | doaj-art-339bf1496784486aa23854c037f6f16e2025-02-03T05:50:19ZengWileyJournal of Toxicology1687-81911687-82052011-01-01201110.1155/2011/109516109516Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas AnalogVictor Paromov0Sudha Kumari1Marianne Brannon2Naga S. Kanaparthy3Hongsong Yang4Milton G. Smith5William L. Stone6Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USADepartment of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USADepartment of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USADepartment of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USADepartment of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USAAmaox, Ltd., 6300 N. Wickham Road 208, Melbourne, FL, USADepartment of Pediatrics, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USASulfur 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.http://dx.doi.org/10.1155/2011/109516 |
| spellingShingle | Victor Paromov Sudha Kumari Marianne Brannon Naga S. Kanaparthy Hongsong Yang Milton G. Smith William L. Stone Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog Journal of Toxicology |
| title | Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog |
| title_full | Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog |
| title_fullStr | Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog |
| title_full_unstemmed | Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog |
| title_short | Protective Effect of Liposome-Encapsulated Glutathione in a Human Epidermal Model Exposed to a Mustard Gas Analog |
| title_sort | protective effect of liposome encapsulated glutathione in a human epidermal model exposed to a mustard gas analog |
| url | http://dx.doi.org/10.1155/2011/109516 |
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