Attenuation of sepsis-induced organ injury in mice by vitamin C

JPEN J Parenter Enteral Nutr. 2014 Sep;38(7):825-39. doi: 10.1177/0148607113497760. Epub 2013 Aug 5.


Background: Multiple organ dysfunction syndrome (MODS) is the principal cause of death in patients with sepsis. Recent work supports the notion that parenteral vitamin C (VitC) is protective in sepsis through pleiotropic mechanisms. Whether suboptimal levels of circulating VitC increase susceptibility to sepsis-induced MODS is unknown.

Materials and methods: Unlike mice, humans lack the ability to synthesize VitC because of loss of L-gulono-γ-lactone oxidase (Gulo), the final enzyme in the biosynthesis of VitC. To examine whether physiological levels of VitC are required for defense against a catastrophic infection, we induced sepsis in VitC sufficient and VitC deficient Gulo(-/-) mice by intraperitoneal infusion of a fecal stem solution (FIP). Some VitC deficient Gulo(-/-) mice received a parenteral infusion of ascorbic acid (AscA, 200 mg/kg) 30 minutes after induction of FIP. We used molecular, histological, and biochemical analyses to assess for MODS as well as abnormalities in the coagulation system and circulating blood cells.

Results: FIP produced injury to lungs, kidneys and liver (MODS) in VitC deficient Gulo(-/-) mice. MODS was not evident in FIP-exposed VitC sufficient Gulo(-/-) mice and attenuated in VitC deficient Gulo(-/-) mice infused with AscA. Septic VitC deficient Gulo(-/-) mice developed significant abnormalities in the coagulation system and circulating blood cells. These were attenuated by VitC sufficiency/infusion in septic Gulo(-/-) mice.

Conclusions: VitC deficient Gulo(-/-) mice were more susceptible to sepsis-induced MODS. VitC sufficiency or parenteral infusion of VitC, following induction of sepsis, normalized physiological functions that attenuated the development of MODS in sepsis.

Keywords: L-gulono-γ-lactone oxidase; coagulation; inflammation; multiple organ dysfunction syndrome; sepsis; vitamin C.

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Ascorbic Acid Deficiency / complications
  • Ascorbic Acid Deficiency / therapy*
  • Blood Cells
  • Blood Coagulation
  • Infusions, Parenteral
  • Kidney
  • L-Gulonolactone Oxidase / deficiency
  • L-Gulonolactone Oxidase / metabolism
  • Liver
  • Lung
  • Mice, Knockout
  • Multiple Organ Failure / etiology
  • Multiple Organ Failure / prevention & control*
  • Sepsis / complications*
  • Vitamins / pharmacology
  • Vitamins / therapeutic use*


  • Vitamins
  • L-Gulonolactone Oxidase
  • Ascorbic Acid