Antioxidant/stress response in mouse epidermis following exposure to nitrogen mustard.

Autor: Wahler G; Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, United States., Heck DE; Department of Environmental Health Science, New York Medical College, Valhalla, NY 10595, United States., Heindel ND; Department of Chemistry, Lehigh University, Bethlehem, PA 18015, United States., Laskin DL; Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, United States., Laskin JD; Department of Environmental and Occupational Health, Rutgers University School of Public Health, Piscataway, NJ 08854, United States., Joseph LB; Department of Pharmacology and Toxicology, Rutgers University Ernest Mario School of Pharmacy, Piscataway, NJ 08854, United States. Electronic address: lbjoseph@pharmacy.rutgers.edu.
Jazyk: angličtina
Zdroj: Experimental and molecular pathology [Exp Mol Pathol] 2020 Jun; Vol. 114, pp. 104410. Date of Electronic Publication: 2020 Feb 28.
DOI: 10.1016/j.yexmp.2020.104410
Abstrakt: Nitrogen mustard (NM) is a highly reactive bifunctional alkylating agent that induces inflammation, edema and blistering in skin. An important mechanism mediating the action of NM and related mustards is oxidative stress. In these studies a modified murine patch-test model was used to analyze DNA damage and the antioxidant/stress response following NM exposure in isolated epidermis. NM (20 μmol) was applied to glass microfiber filters affixed to a shaved dorsal region of skin of CD-1 mice. NM caused structural damage to the stratum corneum as reflected by increases in transepidermal water loss and skin hydration. This was coordinate with edema, mast cell degranulation and epidermal hyperplasia. Within 3 h of NM exposure, a 4-fold increase in phosphorylated histone H2AX, a marker of DNA double-stranded breaks, and a 25-fold increase in phosphorylated p53, a DNA damage marker, were observed in the epidermis. This was associated with a 40% increase in 8-oxo-2'-deoxyguanosine modified DNA in the epidermis and a 4-fold increase in 4-hydroxynonenal modified epidermal proteins. At 12 h post NM, there was a 3-75 fold increase in epidermal expression of antioxidant/stress proteins including heme oxygenase-1, thioredoxin reductase, superoxide dismutase, glutathione reductase, heat shock protein 27 and cyclooxygenase 2. These data indicate that NM induces early oxidative epidermal injury in mouse skin leading to an antioxidant/stress response. Agents that enhance this response may be useful in mitigating mustard-induced skin injury.
Competing Interests: Declaration of Competing Interest The authors have declared that there is no conflict of interest.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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