Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo, 2007
Topics: ascorbic acid ” cancer ” vitamin C ” pharmacokinetics
Authors: Qi Chen, Michael Graham Espey, Andrew Y. Sun, Je-Hyuk Lee, Murali C. Krishna, Emily Shacter, Peter L. Choyke, Chaya Pooput, Kenneth L. Kirk, Garry R. Buettner and Mark Levine
Abstract
Ascorbate (ascorbic acid, vitamin C), in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc*-) and H2O2 in the extracellular space compared with blood. Here we test this hypothesis in vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses (ca 0.25–0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50–100 mikroM in blood and extracellular fluid increased to peaks of >8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of
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