Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Abstract Text:

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,Mark Levine,

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 H(2)O(2) 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 ( approximately 0.25-0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50-100 microM 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 <150 microM in both fluids. In blood, Asc(*-) concentrations measured by EPR were undetectable with oral administration and always <50 nM with parenteral administration, even when corresponding ascorbate concentrations were >8 mM. After parenteral dosing, Asc(*-) concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations. By using the synthesized probe peroxyxanthone, H(2)O(2) in extracellular fluid was detected only after parenteral administration of ascorbate and when Asc(*-) concentrations in extracellular fluid exceeded 100 nM. The data show that pharmacologic ascorbate is a prodrug for preferential steady-state formation of Asc(*-) and H(2)O(2) in the extracellular space but not blood. These data provide a foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent in cancer and infections.

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Publishing Authors By Initials

Q Chen,MG Espey,AY Sun,JH Lee,MC Krishna,E Shacter,PL Choyke,C Pooput,KL Kirk,GR Buettner,M Levine,

For similar animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats research abstracts see: animals: chordata: vertebrates: mammals: rodentia: muridae: murinae: rats research

PUBMED ID PMID:

MEDLINE DATE:

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 8749-54

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 14

MONTH: 05

YEAR: 2007

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Keywords Mesh Terms:

KEYWORDS: Rats

MESH TERMS: metabolism

Chemical & Substance for Abstract: Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Information

Substance Name: Hydrogen Peroxide

Registry Number: 7722-84-1

Grant and Affiliation Information for Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.

AFFILIATION: Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: Z01 DK54506

ACRONYM: DK

MEDLINETA: Proc Natl Acad Sci U S A

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo Related Publications

• Aberrant crypt foci in patients with a positive family history of sporadic colorectal cancer.
• Autophagy gene-dependent clearance of apoptotic cells during embryonic development.
• Cancer and myositis: new insights into an old association.
• Cascade model of ventricular-arterial coupling and arterial-cardiac baroreflex function for cardiovascular variability in humans.
• Chondroblastoma of the temporal bone: consistent middle fossa involvement.
• Daptomycin for infective endocarditis.
• Defects in retinal pigment epithelium cell proliferation and retinal attachment in mutant mice with p27(Kip1) gene ablation.
• Dopamine reduction of GABA currents in striatal medium-sized spiny neurons is mediated principally by the D(1) receptor subtype.
• Dysfunctional channels are making noise in CAG triplet repeat disorders.
• Effects of alcohol on group formation among male social drinkers.
• Energy expenditure of sedentary screen time compared with active screen time for children.
• Evolution of the ventral midline in insect embryos.
• GATA factors participate in tissue-specific immune responses in Drosophila larvae.
• Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing adipose tissue.
• HES6 reverses nuclear reprogramming of insulin-producing cells following cell fusion.
• Left ventricular aneurysmectomy: tailored scar excision and linear closure.
• MDM2 SNP309 accelerates colorectal tumour formation in women.
• MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia.
• Mechanically-evoked C-fiber activity in painful alcohol and AIDS therapy neuropathy in the rat.
• Orexin A mediation of time spent moving in rats: neural mechanisms.
• Pathologic complete response may not represent the optimal surrogate for survival after preoperative therapy for esophageal cancer.
• Professionalism and evolving concepts of quality.
• Reconstruction of complicated skull base defects utilizing free tissue transfer.
• Sources of beta-Cells for Human Cell-Based Therapies for Diabetes.
• Steroid hormone activation of wandering in the isolated nervous system of Manduca sexta.
• Surfactant protein D regulates the cell surface expression of alveolar macrophage beta(2)-integrins.
• The global market for ADHD medications.
• Transfusion related acute lung injury in cardiac surgery.
• TrkA and PKC-epsilon in thermal burn-induced mechanical hyperalgesia in the rat.
• Weekly changes in basal metabolic rate with eight weeks of overfeeding.