Action of the antileukemic and anti-HTLV-III (anti-HIV) agent avarol on the levels of superoxide dismutases and glutathione peroxidase activities in L5178y mouse lymphoma cells.
The antileukemic and anti-HTLV-III (anti-HIV) agent avarol, a sesquiterpenoid hydroquinone, was determined to be converted into its corresponding quinone derivative avarone via the semiquinone free radical. Its g-value was 2.0047; after hyperfine splitting the energy levels revealed 16 isotropic Hfs. The redox reaction products were identified at the pH values 4.0, 7.0 and 12.0 and the overall reaction pathways were formulated. In vivo experiments with L5178y mouse lymphoma cells in the ascites of mice revealed that the cytostatic potencies of avarol and avarone cannot be augmented by lowering the pH value. Incubation studies with L5178y cells in vitro showed that the intracellular levels of superoxide dismutases (SODases) and of glutathione (GSH) peroxidase activities significantly change after avarol administration. While both the Mn-SODase and the Cu/Zn-SODase activities dropped significantly, the GSH peroxidase activity increased inversely. From these experiments we assume that the anti-tumour and the antiviral effects of avarol/avarone may be due to an increase, induced by the drug, of the intracellular concentrations of superoxide radicals.
Batke
E
E
II. Medizinische Klinik, Universität, Mainz, West Germany.
Ogura
R
R
Vaupel
P
P
Hummel
K
K
Kallinowski
F
F
Gasić
M J
MJ
Schröder
H C
HC
Müller
W E
WE
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004578:Electron Spin Resonance Spectroscopy; D005947:Glucose / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006678:HIV / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007940:Leukemia L5178 / Q000201:enzymology*; D007942:Leukemia, Experimental / Q000201:enzymology*; D051379:Mice; D010084:Oxidation-Reduction; D012717:Sesquiterpenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D000998:Antiviral Agents; D012717:Sesquiterpenes; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose; C023663:avarol