Inactivation of mouse epidermal 12-lipoxygenase by anthralin--implications for the role of oxygen radicals.
In activation of 12-lipoxygenase (12-LO) in mouse epidermal homogenate by the antipsoriatic drug anthralin has been studied in detail. In view of the chemical instability of anthralin in a physiological buffer, the biological effects ascribed to the molecule itself may be related to some of its breakdown products. However, the inhibitory activity could not be attributed to the known stable oxidation product of anthralin, danthron, which did not decrease (12-LO activity. Addition of the antioxidants 2,6-di-tert-butyl-4-methylphenol (BHT) or beta-carotene, or the hydroxyl radical scavenger sodium benzoate, protected against anthralin-mediated 12-LO inactivation, suggesting that pro-oxidant species derived from anthralin play a key role in the inhibitory action. Even though inhibitory effects of anthralin against catalase and superoxide dismutase (SOD) have been observed under the conditions applied in this study, these antioxidant enzymes also partially prevented the inhibition of 12-LO by anthralin when added to the incubation mixtures. Control experiments without anthralin revealed that the oxygen radical scavengers and antioxidant enzymes, themselves, did not appreciably influence epidermal 12-LO activity. A mechanism underlying the inactivation of epidermal 12-LO by anthralin is proposed, which involves active oxygen species formed during the auto-oxidation of the drug.
Müller
K
K
Institut für Pharmazie, Universität Regensburg, Germany.
Gawlik
I
I
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000875:Anthralin / Q000494:pharmacology*; D000880:Anthraquinones / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D016859:Lipoxygenase Inhibitors; D051379:Mice; D010100:Oxygen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
D000873:Anthracenes; D000880:Anthraquinones; D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D016859:Lipoxygenase Inhibitors; C099596:bianthrone; D002374:Catalase; D013482:Superoxide Dismutase; D010100:Oxygen; D000875:Anthralin; C004315:danthron