Attenuation of Sepsis-Induced Organ Injury in Mice by Vitamin C

作者：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^*

来源：Journal of Parenteral and Enteral Nutrition, 2014, 38(7): 825-839.

DOI：10.1177/0148607113497760

• vitamin C
• sepsis
• multiple organ dysfunction syndrome
• L-gulono--lactone oxidase
• inflammation
• coagulation

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--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.

• 出版日期2014-9