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Antioxidants attenuate anthralin-induced skin inflammation in BALB/c mice: role of specific proinflammatory cytokines.
Lange RW; Germolec DR; Foley JF; Luster MI
J Leukoc Biol 1998 Aug; 64(2):170-176
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.
Antioxidants; Antioxidation; Skin-disorders; Therapeutic-agents; Toxic-effects; Skin-irritants; Laboratory-animals; Animals; Animal-studies; Free-radicals; Free-radical-generation; Author Keywords: anthralin skin lesions; free radical generation; reactive oxygen intermediates
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
Issue of Publication
Journal of Leukocyte Biology
WV; PA; NC
Page last reviewed: September 2, 2020Content source: National Institute for Occupational Safety and Health Education and Information Division