Attenuation of Sepsis-Induced Organ Injury in Mice by Vitamin C. (September 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: JPEN, Journal of parenteral and enteral nutrition. Volume 38:Number 7(2014)
• Page Start: 825
• Page End: 839
• Publication Date: 2014-09
• Subjects: vitamin C -- sepsis -- multiple organ dysfunction syndrome -- L-gulono-γ-lactone oxidase -- inflammation -- coagulation; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; 615.85484
• DOI: 10.1177/0148607113497760
• Languages: English
• ISSNs: 0148-6071

Abstract

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.