INACTIVATION OF MOUSE EPIDERMAL 12-LIPOXYGENASE BY ANTHRALIN - IMPLICATIONS FOR THE ROLE OF OXYGEN RADICALS

Inactivation of 12-lipoxygenase (12-LO) in mouse epidermal homogenate by the antipsoriatic drug anthralin has been studied in detail. In vie w 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 co uld not be attributed to the known stable oxidation product of anthral in, danthron, which did not decrease 12-LO activity. Addition of the a ntioxidants 2,6-di-tert-butyl-4-methylphenol (BHT) or beta-carotene, o r the hydroxyl radical scavenger sodium benzoate, protected against an thralin-mediated 12-LO inactivation, suggesting that pro-oxidant speci es derived from anthralin play a key role in the inhibitory action. Ev en though inhibitory effects of anthralin against catalase and superox ide dismutase (SOD) have been observed under the conditions applied in this study, these antioxidant enzymes also partially prevented the in hibition 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 i nfluence epidermal 12-LO activity. A mechanism underlying the inactiva tion of epidermal 12-LO by anthralin is proposed, which involves activ e oxygen species formed during the auto oxidation of the drug.