Mechanism of action of vitamin C in sepsis: Ascorbate modulates redox signaling in endothelium

Abstract

Circulating levels of vitamin C (ascorbate) are low in patients with sepsis. Parenteral administration of ascorbate raises plasma and tissue concentrations of the vitamin and may decrease morbidity. In animal models of sepsis, intravenous ascorbate injection increases survival and protects several microvascular functions, namely, capillary blood flow, microvascular permeability barrier, and arteriolar responsiveness to vasoconstrictors and vasodilators. The effects of parenteral ascorbate on microvascular function are both rapid and persistent. Ascorbate quickly accumulates in microvascular endothelial cells, scavenges reactive oxygen species, and acts through tetrahydrobiopterin to stimulate nitric oxide production by endothelial nitric oxide synthase. A major reason for the long duration of the improvement in microvascular function is that cells retain high levels of ascorbate, which alter redox-sensitive signaling pathways to diminish septic induction of NADPH oxidase and inducible nitric oxide synthase. These observations are consistent with the hypothesis that microvascular function in sepsis may be improved by parenteral administration of ascorbate as an adjuvant therapy.

Role of Mitochondrial Oxidative Stress in Sepsis

“…Plasma AA in patients with multiorgan failure was significantly lower [34], whereas low concentrations were inversely correlated with increased lipid peroxides [69] a marker of increased oxidative stress. Results from animal models demonstrated that AA ameliorates edema and hypotension and improves arteriolar responsiveness and capillary blood flow [70][71][72][73]. Experiments in healthy volunteers after induction of systemic inflammation by low doses of E. coli endotoxemia revealed that the hyporeactivity can be corrected by high doses of vitamin C, suggesting that oxidative stress may represent an important target for inflammation-induced impaired vascular function [74].…”

Suppression of lipopolysaccharide-induced expression of inflammatory indicators in RAW 264.7 macrophage cells by extract prepared fromGinkgo bilobacambial meristematic cells

“…We presume the phenolic compounds included in the fractionated samples from ginkgo-derived CMCs may be responsible for their anti-inflammatory and antioxidative properties (Ríos et al, 2009;Wilson, 2009). Polyphenolic compounds including catechin, quercetin, myricetin, and myricetin-rutinosides are identified as the main components of ethanol extract from many plants (Zhao et al, 2007).…”

Effects of the Antioxidant-Enriched Concentrated Liquid Diet ANOM on Oxidative Stress and Multiple Organ Injury in Patients with Septic Shock: A Pilot Study

“…In addition, many reports have reported the efficacy of the water-soluble antioxidant vitamin C for treating sepsis [5,13,[28][29][30][31]. Although copper and zinc, which bind to the superoxide dismutase active center, are essential for maintaining the antioxidant system, these trace elements have not been studied clinically in septic shock patients [27].…”