Ascorbate enhances the toxicity of the photodynamic action of Verteporfin in HL-60 cells.

Free Radical Biology & Medicine
Galina G KramarenkoFreya Q Schafer

Abstract

As a reducing agent, ascorbate serves as an antioxidant. However, its reducing function can in some settings initiate an oxidation cascade, i.e., seem to be a "pro-oxidant." This dichotomy also seems to hold when ascorbate is present during photosensitization. Ascorbate can react with singlet oxygen, producing hydrogen peroxide. Thus, if ascorbate is present during photosensitization the formation of highly diffusible hydrogen peroxide could enhance the toxicity of the photodynamic action. On the other hand, ascorbate could decrease toxicity by converting highly reactive singlet oxygen to less reactive hydrogen peroxide, which can be removed via peroxide-removing systems such as glutathione and catalase. To test the influence of ascorbate on photodynamic treatment we incubated leukemia cells (HL-60 and U937) with ascorbate and a photosensitizer (Verteporfin; VP) and examined ascorbic acid monoanion uptake, levels of glutathione, changes in membrane permeability, cell growth, and toxicity. Accumulation of VP was similar in each cell line. Under our experimental conditions, HL-60 cells were found to accumulate less ascorbate and have lower levels of intracellular GSH compared to U937 cells. Without added ascorbate, HL-60 cells we...Continue Reading

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Aug 11, 2006·Journal of Cell Science·Amina A Qutub, Aleksander S Popel
Apr 4, 2012·Molecular Medicine Reports·Christina M HardawayKaram F A Soliman
May 9, 2012·Journal of Photochemistry and Photobiology. A, Chemistry·Pedro Sanchez-CruzAntonio E Alegria
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Feb 4, 2014·Journal of Biochemical and Molecular Toxicology·Hang QiYoshimasa Nakamura
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Aug 13, 2013·Redox Biology·Brett A WagnerGarry R Buettner
Feb 20, 2016·Chembiochem : a European Journal of Chemical Biology·Helder Tão SoaresLuis G Arnaut

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