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Attenuation of Sepsis‐Induced Organ Injury in Mice by Vitamin C
Author(s) -
Fisher Bernard J.,
Kraskauskas Donatas,
Martin Erika J.,
Farkas Daniela,
Puri Puneet,
Massey H. Davis,
Idowu Michael O.,
Brophy Donald F.,
Voelkel Norbert F.,
Fowler Alpha A.,
Natarajan Ramesh
Publication year - 2014
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607113497760
Subject(s) - sepsis , medicine , vitamin c , ascorbic acid , organ dysfunction , immunology , gastroenterology , biology , food science
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.