Antioxidants Attenuate Anthralin-Induced Skin Inflammation in BALB/C Mice: Role of Specific Proinflammatory Cytokines

Details

• Personal Author:
  Foley JF ; Germolec DR ; Lange RW ; Luster MI
• Description:
  Anthralin is the most common therapeutic agent among a small number of pro-oxidant, 9-anthrones effective in the topical treatment of psoriasis. However, the usefulness of this drug is diminished by toxic side effects, including skin irritation and inflammation. The activities of anthralin are believed to be mediated by the generation of reactive oxygen intermediates and anthrone radicals produced in the skin. In this study, the dermal inflammatory response to anthralin was determined using a mouse ear swelling test. Maximum ear swelling induced by anthralin coincided with the elevation of cytokine mRNA expression in the skin, including interleukin-6, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, and tumor necrosis factor alpha at 24 h post challenge. The role of free radical generation in ear swelling and cytokine modulation were examined by systemic administration of cell permeable and impermeable antioxidants before anthralin challenge. Superoxide dismutase and alpha-tocopherol acetate, but not the glutathione precursor N-acetyl cysteine, were effective inhibitors of anthralin-induced ear swelling and cytokine elevation. Maximum inflammatory cell infiltration occurred 72-96 h post anthralin challenge and was also reduced by antioxidants. These data suggest that oxidative stress, generated at the site of anthralin treatment, alters the expression of dermal chemokines and other cytokines resulting in the recruitment of inflammatory cells. Systemic antioxidant administration may provide opportunities for therapeutic intervention against anthralin-associated toxicities. [Description provided by NIOSH]
• Subjects:
  Animals Antioxidants Free Radicals Hazardous Substances Laboratories Occupational Health Safety Skin Skin Diseases
• Keywords:
  Animal-studies Antioxidation Author Keywords: Anthralin Skin Lesions Free-radical-generation Free-radicals Free Radical Generation Laboratory-animals Reactive Oxygen Intermediates Skin-disorders Skin-irritants Therapeutic-agents Toxic-effects

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• ISSN:
  0741-5400
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  North Carolina ; OSHA Region 3 ; OSHA Region 4 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  170-176
• Volume:
  64
• Issue:
  2
• NIOSHTIC Number:
  nn:20025489
• Citation:
  J Leukoc Biol 1998 Aug; 64(2):170-176
• Contact Point Address:
  Robert W. Lange, Ph.D., University of Pittsburgh Graduate School of Public Health, Department of Environmental and Occupational Health, RIDC Park, 260 Kappa Drive, Pittsburgh, PA 15238
• Email:
  lange@vms.cis.pitt.edu
• Federal Fiscal Year:
  1998
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Leukocyte Biology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c6ea0c169b4b03c810fd95ceeae878fe17beb4b232b459eb3b215acd0b7e43df64926332c5e48b480c8879f378a6860f728a7adf59403bd3b6fdf8f12d92ea04
• Download URL:
  https://stacks.cdc.gov/view/cdc/196833/cdc_196833_DS1.pdf
• File Type:
  [PDF - 361.03 KB ]