Antioxidant and Prooxidant effects of the Antipsoriatic Compound Anthralin in Skin and Subcellular Fractions
Anthralin (1.8-dihydroxy-9-anthrone) is a potent antipsoriatic compound (Ashton 1983). External therapy of psoriasis with anthralin has been introduced by Galewsky in 1916 and structure activity relationship of anthralin derivatives was first studied by Unna. The minimal structure for antipsoriatic activity of anthrone compounds has been defined by Krebs and corresponds to 1- hydroxy -9- anthrone (Krebs 1969). It contains I) a hydroxyl group in position 1, II) a carbonyl group in position 9, and III) two hydrogen groups in position 10. Altering only one group results in loss of antipsoriatic activity. Anthralin is a strong reductant that is readily oxidized by light, trace concentrations of metal ions and oxygen. Reactive oxygen species (singlet oxygen, Superoxide anion and the hydroxyl radical) are formed as reaction intermediates during oxidation of anthralin. The anthralin metabolites anthraquinone and anthralin dimer have been identified in human and rat skin. A significant portion of anthralin is converted in intact skin into an ether insoluble product (Cavey 1985) which is assigned to anthralin “dark structures” (Mustakallio 1984). Anthralin dark structures are not well characterized chemically, naphtodianthrones and other polycyclic aromatic hydrocarbons are constituents of this product. A persistent free radical was detected in pig skin treated with anthralin, and it was suggested that the 10-anthranyl radical is the species reported (Shroot 1986). Anthralin binds to the plasma membrane of keratinocytes and is subsequently accumulated in mitochondria. It inhibits oxygen consumption in keratinocytes, fìbroblasts, yeast and ascites cells and in skin. Research into mechanism of action of anthralin has elucidated mainly four target sites: 1) alteration of mitochondrial functions, 2) inhibition of cellular key enzymes, 3) interaction with nucleic acid metabolism, and 4) modulation of neutrophil function and arachidonic acid metabolism.
KeywordsFree Radical Formation Hairless Mouse Quinone Reductase Lipid Peroxide Formation Redox Component
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