Dithranol, glucose-6-phosphate dehydrogenase inhibition and active oxygen species.
Inhibition of glucose-6-phosphate dehydrogenase (G6-PDH) by dithranol (anthralin, CAS 480-22-8) has been studied in the presence of catalase, superoxide dismutase (SOD) and various scavengers of active oxygen species. Most scavengers were found to be either inhibitors of G6-PDH by themselves or simply without effect. The combined addition of catalase and SOD as well as the heat-denatured enzymes and the oxygen radical scavengers alpha-tocopherol and salicylic acid markedly reduced the inhibitory effect of dithranol. The direct exposure of G6-PDH to active oxygen species led to different results. When liberated from a water-soluble naphthalene endoperoxide, singlet oxygen was without effect whereas photosensitization with methylene blue resulted in a total loss of enzyme activity. Experiments under anaerobic conditions revealed that this inhibition was accomplished by the triplet state of the sensitizer. Superoxide anion radical was highly effective at concentrations corresponding to the amount of that produced by a 10 mumol/l dithranol solution. In contrast, hydroxyl, alkylperoxyl and alkoxyl radicals were all less efficient. H2O2 and alkylhydroperoxides did not alter the enzyme activity. The results suggest that .O2- is the potent species towards G6-PDH, if dithranol acts through formation of active oxygen species.
Müller
K
K
Institute of Pharmacy, University of Regensburg, Fed. Rep. of Germany.
Seidel
M
M
Braun
C
C
Zieresi
K
K
Wiegrebe
W
W
D000693:Anaerobiosis; D000875:Anthralin / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D016166:Free Radical Scavengers; D005609:Free Radicals; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D008751:Methylene Blue / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology*; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D016166:Free Radical Scavengers; D005609:Free Radicals; D012459:Salicylates; D014810:Vitamin E; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D020156:Salicylic Acid; D010100:Oxygen; D008751:Methylene Blue; D000875:Anthralin