Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin

Kuck, Jamie L.; Bastarache, Julie A.; Shaver, Ciara M.; Fessel, Joshua P.; Dikalov, Sergey; May, James M.; Ware, Lorraine B.

doi:10.1016/j.bbrc.2017.11.058

Cited by 45 publications

(42 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…13 Sera from GVHD patients induces expression of adhesion molecules VCAM-1, ICAM-1, and von Willebrand factor on in vitro endothelial cell cultures, suggesting an important link between endothelial dysfunction and alloreactive tissue injury. 14 Ascorbic acid applied in the clinical appropriate clinical settings attenuates endothelial dysfunction induced by provocations such as ischemia-reperfusion injury, 15,16 cell free hemoglobin, 17 and sepsis. 18,19 Ascorbic acid prevents reactive oxygen species generation through the NADPH oxidase, inducible NO synthase, and by reductive recycling of tetrahydrobiopterin.…”

Section: Discussionmentioning

confidence: 99%

“…Ascorbic acid is an effective antiinflammatory agent with its demonstrated ability to inhibit NF-kB-driven inflammatory cytokines IL-6, IL-8, and TNF-a expression, and by its ability to enhance vasodilator nitric oxide (NO) production. 5,6 Further, hypovitaminosis C is well described in critically ill patients. In this population, intravenous ascorbic acid increases nitric oxide bioavailability in the microcirculation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Rasheed

Simmons

Fisher

et al. 2019

Preprint

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Rasheed

Simmons

Fisher

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Ascorbic acid applied in the appropriate clinical settings attenuates endothelial dysfunction induced by provocations such as ischemia‐reperfusion injury, cell‐free hemoglobin, and sepsis . Ascorbic acid exerts a protective effect on vascular endothelium through several different pathways, including collagen synthesis, prevention of reactive oxygen species generation through the NADPH oxidase, inducible NO synthase and prevention of its scavenging by superoxide radicals, as well as by reductive recycling of tetrahydrobiopterin .…”

Section: Discussionmentioning

confidence: 99%

“…Ascorbic acid is an effective anti-inflammatory agent with its demonstrated ability to inhibit NF-kB-driven inflammatory cytokines IL-6, IL-8, and TNF-α expression, and by its ability to enhance vasodilator nitric oxide (NO) production. 5,6 Further, hypovitaminosis C is well described in critically ill patients, who have several parallels with HCT patients, such as, elevation of biomarkers including CRP and citrulline, as well as inflammatory cytokines such as TNFα, IL-1, and IL-6. [7][8][9][10] In this population, intravenous ascorbic acid increases nitric oxide bioavailability in the microcirculation.…”

Section: Introductionmentioning

confidence: 99%

“…Sera from GVHD patients induces expression of adhesion molecules VCAM-1, ICAM-1, and von Willebrand factor on in vitro endothelial cell cultures, suggesting an important link between endothelial dysfunction and alloreactive tissue injury 3. Ascorbic acid applied in the appropriate clinical settings attenuates endothelial dysfunction induced by provocations such as ischemia-reperfusion injury,21,22 cell-free hemoglobin,6 and sepsis 23,24. Ascorbic acid exerts a protective effect on vascular endothelium through several different pathways, including collagen synthesis,25 prevention of reactive oxygen species generation through the NADPH oxidase, inducible NO synthase and prevention of its scavenging by superoxide radicals, as well as by reductive recycling of tetrahydrobiopterin 26,27.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Reduced plasma ascorbic acid levels in recipients of myeloablative conditioning and hematopoietic cell transplantation

Rasheed

Simmons

Fisher

et al. 2019

European J of Haematology

View full text Add to dashboard Cite

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 four autologous HCT). Ascorbate levels declined postconditioning to 27.3 μMol/L (±14.1) by day 0 (P = .03 compared with pretransplant baseline), reaching a nadir level of 21.5 (±13.8) on day 14 (P = .003) post‐transplant. Patients undergoing allogeneic HCT continued to have low AA levels to day 60 post‐transplant. 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.

show abstract

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

et al. 2023

View full text Add to dashboard Cite

ImportanceSepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.ObjectiveTo describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.Design, Setting, and ParticipantsThis prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.InterventionsThe intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.Main Outcomes and MeasuresCognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.ResultsAfter exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.Conclusions and RelevanceIn survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.Trial RegistrationClinicalTrials.gov Identifier: NCT03509350

show abstract

Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin

Abstract: CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis.

Cited by 45 publications

References 29 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

Reduced plasma ascorbic acid levels in recipients of myeloablative conditioning and hematopoietic cell transplantation

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors

Contact Info

Product

Resources

About