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Ascorbate Is a Primary Antioxidant in Mammals.

Junichi Fujii1, Tsukasa Osaki1, Tomoki Bo2

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Summary

Vitamin C (ascorbate) acts as an antioxidant and enzyme cofactor. Studies using genetically modified mice reveal its crucial role in protecting against oxidative stress and potentially preventing cancer.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Nutritional Science

Background:

  • Ascorbate (vitamin C) is essential for primates, acting as an enzyme cofactor (e.g., prolyl hydroxylases) and an antioxidant.
  • Its physiological roles are complex due to interactions with other redox systems and potential pro-oxidant effects.
  • Most mammals synthesize ascorbate from glucose, complicating direct study of its functions.

Purpose of the Study:

  • To investigate the physiological roles of ascorbate, particularly its antioxidant and potential anti-cancer functions.
  • To overcome challenges in studying ascorbate's effects in mammals that can synthesize it.

Main Methods:

  • Utilized genetically modified mice lacking key genes for ascorbate synthesis (GULO, RGN, AKR1A).
  • Employed ascorbate transporter (SVCT)-deficient mice models.
  • Investigated the effects of ascorbate and dehydroascorbate in various biological contexts.

Main Results:

  • Studies using ascorbate synthesis-deficient mice and SVCT-deficient mice strongly support ascorbate's protective role against oxidative damage.
  • Combined effects of ascorbate on epigenetics and antioxidation appear to inhibit cancer development.
  • Pharmacological concentrations of ascorbate and dehydroascorbate demonstrated redox-dependent tumoricidal activity.

Conclusions:

  • Ascorbate plays a vital role in combating oxidative stress.
  • Ascorbate's dual action in epigenetic regulation and antioxidation shows promise in cancer prevention.
  • High-dose ascorbate may offer a therapeutic strategy against tumors via redox mechanisms.