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Müller, K. ; Seidel, M. ; Braun, C. ; Ziereis, K. ; Wiegrebe, Wolfgang

Dithranol, Glucose-6-phosphate Dehydrogenase Inhibition and Active Oxygen Species

Article

Müller, K., Seidel, M., Braun, C., Ziereis, K. and Wiegrebe, Wolfgang (1991) Dithranol, Glucose-6-phosphate Dehydrogenase Inhibition and Active Oxygen Species. Arzneimittel-Forschung 41 (11), pp. 1176-1181.

DOI to cite this document: 10.5283/epub.15735


Abstract

Inhibition of glucose-6-phosphate dehydrogenase (G6- PDH) by dithranpl (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 heatdenatured enzymes ...

Inhibition of glucose-6-phosphate dehydrogenase (G6-
PDH) by dithranpl (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 heatdenatured
enzymes and the oxygen radical scavengers atocopherol
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 nmol/l dithranol solution.
In contrast, hydroxyl, alkylperoxyl and alkoxyl radicals
were all less efficient. H202 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.

Glucose-6-phosphat-Dehydrogenase (G6-PDH)-Hemmung
durch Dithranol (Anthralin, CAS 480-22-8) wurde
in Gegenwart von Catalase, Superoxid-Dismutase (SOD)
und verschiedenen Fängern für aktive Sauerstoffspezies
untersucht. Die meisten Fänger waren entweder selbst
Hemmstoffe der G6-PDH oder wirkungslos. Sowohl die
kombinierte Zugabe von Catalase und SOD als auch die
denaturierten Enzyme, ebenso die Sauerstoffradikalfänger
a-Tocopherol und Salicylsäure zeigten eine deutliche
Reduzierung der durch Dithranol verursachten Hemmefi
fekte. Die direkte Einwirkung von aktiven Sauerstoffspezies
auf G6-PDH führte zu unterschiedlichen Resultaten.
Freisetzung von Singulett-Sauerstoff aus einem wasserlöslichen
Endoperoxid war ohne Effekt, hingegen führte
die Photosensibilisierung mit Methylenblau zum vollständigen
Verlust der Enzymaktivität. Experimente unter anaeroben
Bedingungen zeigten jedoch, daß diese Hemmung
durch den Triplett-Zustand des Sensibilisators verursacht
wurde. Superoxid-Anion-Radikal erwies sich in
Konzentrationen, die von einer 10 jumol/l Dithranol-Lösung
produziert werden, als hochwirksam. Hydroxyl-,
Alkylperoxyl- und Alkoxyl-Radikale waren hingegen weniger
wirksam. H202 und Alkylhydroperoxide führten zu
keiner Beeinträchtigung der Enzymaktivität. Die Resultate
deuten darauf hin, daß O2 die potente Spezies der
G6-PDH-Hemmung durch Dithranol ist, wenn diese über
die aktiven Sauerstoffspezies erfolgt


Involved Institutions


Details

Item typeArticle
Journal or Publication TitleArzneimittel-Forschung
Volume41
Number of Issue or Book Chapter11
Page Rangepp. 1176-1181
Date1991
Date of publication12 Jul 2010 05:14
InstitutionsChemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Wiegrebe
KeywordsAnthralin, in vitro studies • Antipsoriatic drugs • CAS 480-22-8 • Dithranol • Free radicals • Glucose-6-phosphate dehydrogenase, inhibition
Dewey Decimal Classification500 Science > 540 Chemistry & allied sciences
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgUnknown
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-157353
Item ID15735

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