There’s life in the old dog yet: vitamin C as a therapeutic option in endothelial dysfunction

Rodemeister, Sandra; Biesalski, Hans Konrad

doi:10.1186/s13054-014-0461-9

Cited by 10 publications

(8 citation statements)

References 12 publications

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“…18,19 Ascorbic acid prevents reactive oxygen species generation through the NADPH oxidase, inducible NO synthase, and by reductive recycling of tetrahydrobiopterin. 20 These effects occur when high doses of ascorbic acid are administered intravenously as in the sepsis trial recently reported by Fowler et al 21 Furthermore, high dose intravenous AA significantly reduces both vasopressor requirements as well as 28-day mortality in surgical critically ill patients. 22 In patients with sepsis treated with intravenous AA significant reductions in C reactive protein and thrombomodulin occurred which suggests reduced inflammation and reduced vascular injury.…”

Section: Discussionmentioning

confidence: 98%

Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation

Rasheed

Simmons

Fisher

et al. 2019

Preprint

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Hematopoietic cell transplantation (HCT) conditioned using myeloablative conditioning (MAC) is complicated by end organ injury due to endothelial dysfunction and graft versus host disease. Mucositis and oxidant injury results in micronutrient deficiency. Ascorbic acid (AA) levels were measured in 15 patients undergoing HCT conditioned with MAC (11 allogeneic and 4 autologous HCT). Ascorbate levels declined post conditioning to 27.3 (±14.1) by day 0 (p <0.05 compared with baseline), reaching a nadir level of 21.5 (±13.8) on day 14 (p <0.05) posttransplant. Patients undergoing allogeneic HCT continued to have low AA levels to day 60 post transplant, whereas recipients of autologous HCT recovered plasma AA levels to normal. The role of AA in maintaining endothelial function and hematopoietic as well as T cell recovery is provided, developing the rationale for repletion of vitamin C following HCT.

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Section: Discussionmentioning

confidence: 98%

Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation

Rasheed

Simmons

Fisher

et al. 2019

Preprint

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“…Moreover, healthy platelets incubated with septic serum results in post-trascriptional changes including tissue factor pre-mRNA splicing that could be involved in increasing pro-coagulant activity in sepsis [ 57 ]. Interesting new evidence of the possible benefit of antioxidants and radical oxygen species scavengers (e.g., high doses of intravenous vitamin C in septic shock [ 58 ]) have recently been published and appear promising [ 59 , 60 ]. However, further studies on reversal of mitochondrial dysfunction in sepsis are needed.…”

Section: Mechanisms Of Platelet-mediated Organ Damage In Sepsismentioning

confidence: 99%

Platelets and Multi-Organ Failure in Sepsis

Greco

Lupia

Bosco

et al. 2017

IJMS

139

104

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Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

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“…Irrespective of these giants contribution, interest in ascorbic acid use in diseases and cancer in particular went down. Recently one can see the revival of ascorbic acid and has shown many promising directions ranging from cancer to septic shock (13,208) and to reach high plasma levels of ascorbic acid it has to be used intravenously (209).…”

Section: Pauling Gyorgyi Warburg and Ascorbic Acidmentioning

confidence: 99%

Fundamental role of warburg effect in various pathophysiological processes

Vasanthakumar¹

2018

Int J Clin Exp Physiol

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In this review article, the role of Warburg effect in various pathologies will be discussed using septic shock as the base model. I had proposed a slightly extended Warburg effect which I would like to call it as 'Warburg common pathogenesis model or Warburg differentiation dedifferentiation effect', which has the potential to explain septic shock and sepsis associated multi-organ dysfunction and many other major pathologies like SHT, PAH, CHF, DM, Asthma, ARDS, AKI implying most of the diseases may have a common pathogenesis as the underlying mechanism. Increased Nitric oxide (NO) in sepsis via iNOS or any respiratory poison in general irreversibly inhibits the mitochondrial respiration and shifts the metabolic phenotype of the cell from oxidative phosphorylation (OXPHOS) to glycolytic phenotype and the change in metabolic phenotype is followed by the change in cell phenotype from the normal adult dynamic differentiation state to irreversible dedifferentiation statesembryonic phenotype, synthetic / proliferative phenotype, and cancer phenotype. This dedifferentiated state switching can be seen as the cells local survival strategy in response to injuries, but returning to their primitive forms leads to disorder and ends in global collapse of the organ systems and organism which requires order in terms of differentiation. Treatment in most of pathologies should aim at reversing Warburg effect by activation of mitochondrial respiration thereby decreasing the aerobic glycolysis and changing the cell to its normal adult dynamic differentiation phenotype i.e. all the drugs will be used here as differentiation therapy. Adrenergic blockers and Ascorbic acid may be the main treatment options, which are already used by some research groups, other options will be discussed in this article. Even though high NO via iNOS was involved in most of the pathologies including sepsis, any substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation effect may be necessary for normal functioning and the same effect in exaggerated and irreversible way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the diseases including septic shock.

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There’s life in the old dog yet: vitamin C as a therapeutic option in endothelial dysfunction

Cited by 10 publications

References 12 publications

Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation

Reduced Plasma Ascorbic Acid Levels in Recipients of Myeloablative Conditioning & Hematopoietic Cell Transplantation

Platelets and Multi-Organ Failure in Sepsis

Fundamental role of warburg effect in various pathophysiological processes

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