Effect of metals and their antagonists on the radical intensity and cytotoxicity of ascorbates.
Five heavy metal antagonists were compared for their specificity of chelating action against copper (CuCl, CuCl2) and iron (FeCl2, FeCl3). ESR spectroscopy showed that both copper and iron significantly enhanced the radical intensity of ascorbate and sodium 5,6-benzylidene-L-ascorbate (SBA). Equimolar concentrations of dimercaprol efficiently chelated all these metals, thus significantly reducing their stimulation effects. On the other hand, the chelating action of penicillamine, ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid was limited to CuCl and CuCl2 whereas deferoxamine mesylate (DFO) was a specific iron chelator. The cytotoxic activity of sodium ascorbate was augmented by DFO, but diminished by FeCl3. The simultaneous addition of DFO and FeCl3 counteracted each other, thus neutralizing their individual effects. The cytotoxic activity of both sodium ascorbate and SBA was significantly enhanced by CuCl2 and this stimulation effect of CuCl2 was effectively chelated by DTPA. The present study demonstrates the specificity of the chelating action of these five antagonists, suggesting the possible application of these different types of antagonists for the prevention of the pathogenic diseases catalyzed by the corresponding metals.
Satoh
K
K
Analysis Center, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Ida
Y
Y
Kochi
M
M
Tajima
M
M
Kashimata
M
M
Sakagami
H
H
D001205:Ascorbic Acid / Q000037:antagonists & inhibitors*; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D005609:Free Radicals; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007501:Iron / Q000494:pharmacology; D008670:Metals / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002614:Chelating Agents; D005609:Free Radicals; D008670:Metals; D003300:Copper; D007501:Iron; D001205:Ascorbic Acid