ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2015
High-dose ascorbate with low-dose amphotericin B attenuates severity of disease in a model of the reappearance of candidemia during sepsis in the mouse.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Vitamin C enhances corneal fungal infection treatment in mice via chemotaxis and anti-inflammation.Antimicrobial agents and chemotherapy · 2026Article
- Immune suppressive activities of low-density neutrophils in sepsis and potential use as a novel biomarker of sepsis-induced immune suppression.Scientific reports · 2025Article
- Less Severe Polymicrobial Sepsis in ConditionalInternational journal of molecular sciences · 2023Article
- Less Severe Lipopolysaccharide-Induced Inflammation in ConditionalInternational journal of molecular sciences · 2023Article
- Less Severe Sepsis in Cecal Ligation and Puncture Models with and without Lipopolysaccharide in Mice with ConditionalInternational journal of molecular sciences · 2023Article
- The Regulatory Roles ofInternational journal of molecular sciences · 2023Article
- Lipopolysaccharide Tolerance Enhances Murine Norovirus Reactivation: An Impact of Macrophages Mainly Evaluated by Proteomic Analysis.International journal of molecular sciences · 2023Article
- High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions.Biomedicines · 2022Review
- Macrophage depletion alters bacterial gut microbiota partly through fungal overgrowth in feces that worsens cecal ligation and puncture sepsis mice.Scientific reports · 2022Article
- More Prominent Inflammatory Response to Pachyman than to Whole-Glucan Particle and Oat-β-Glucans in Dextran Sulfate-Induced Mucositis Mice and Mouse Injection through Proinflammatory Macrophages.International journal of molecular sciences · 2022Article
- Tubule-mitophagic secretion of SerpinG1 reprograms macrophages to instruct anti-septic acute kidney injury efficacy of high-dose ascorbate mediated by NRF2 transactivation.International journal of biological sciences · 2022Article
- Efficacy and Pharmacokinetics of Fosmanogepix (APX001) in the Treatment ofAntimicrobial agents and chemotherapy · 2021Article
- Prominent Indomethacin-Induced Enteropathy in FcgriibInternational journal of molecular sciences · 2021Article
- A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps inJournal of inflammation research · 2021Article
- Dysregulation of Lipid Metabolism in Macrophages Is Responsible for Severe Endotoxin Tolerance in FcgRIIB-Deficient Lupus Mice.Frontiers in immunology · 2020Article
- Pathogen-Associated Molecules from Gut Translocation Enhance Severity of Cecal Ligation and Puncture Sepsis in Iron-Overload β-Thalassemia Mice.Journal of inflammation research · 2020Article
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- Decreased Protein Kinase C-β Type II Associated with the Prominent Endotoxin Exhaustion in the Macrophage of FcGRIIb-/- Lupus Prone Mice is Revealed by Phosphoproteomic Analysis.International journal of molecular sciences · 2019Article
- The Synergy of Endotoxin and (1→3)-β-D-Glucan, from Gut Translocation, Worsens Sepsis Severity in a Lupus Model of Fc Gamma Receptor IIb-Deficient Mice.Journal of innate immunity · 2018Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Amphotericin B (Ampho B) isa fungicidal drug that causes cell wall injury. Pharmacological ascorbate induces the extracellular prooxidants, which might enter the Ampho B-induced cell wall porosity and act synergistically.W e tested low-dose Ampho B with a short course of pharmacological ascorbate using a mouse model of sepsis preconditioned with an injection of Candida albicans 6 h prior to cecal ligation and puncture (CLP). In this model, candidemia reappeared as early as 6 h after CLP with a predictably high mortality rate. This characteristic mimics sepsis in the phase of immunosuppression inpatients. Using the model, at 12- and 18-h post-CLP, we administered isotonic (pH neutralized) pharmacological ascorbate intravenously with low-dose Ampho B or sodium deoxycholate, vehicle-controlled, administered IP. The survival rate of low-dose Ampho B plus ascorbate was 53%, compared with < 11% for low-dose Ampho B or high-dose Ampho B alone. In addition, a beneficial effect was demonstrated in terms of kidney damage,liver injury, spleen histopathology, and serum markers at 24 h after CLP. Kidney injury was less severe in low-dose Ampho B plus ascorbate combination therapy due to less severe sepsis. Moreover, ascorbate enhanced the effectiveness of phagocytosis against C. albicans in human phagocytic cells. Taken together, the data indicate that the new mouse model simulates sepsis-induced immunosuppression and that the combination of pharmacological ascorbate with an antifungal drug is a potentially effective treatment that may reduce nephrotoxicity, and perhaps also increase fungicidal activity in patients with systemic candidiasis caused by Candida albicans.
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