Ascorbate Is a Primary Antioxidant in Mammals

Abstract

Ascorbate (vitamin C in primates) functions as a cofactor for a number of enzymatic reactions represented by prolyl hydroxylases and as an antioxidant due to its ability to donate electrons, which is mostly accomplished through non-enzymatic reaction in mammals. Ascorbate directly reacts with radical species and is converted to ascorbyl radical followed by dehydroascorbate. Ambiguities in physiological relevance of ascorbate observed during in vivo situations could be attributed in part to presence of other redox systems and the pro-oxidant properties of ascorbate. Most mammals are able to synthesize ascorbate from glucose, which is also considered to be an obstacle to verify its action. In addition to animals with natural deficiency in the ascorbate synthesis, such as guinea pigs and ODS rats, three strains of mice with genetic removal of the responsive genes (GULO, RGN, or AKR1A) for the ascorbate synthesis have been established and are being used to investigate the physiological roles of ascorbate. Studies using these mice, along with ascorbate transporter (SVCT)-deficient mice, largely support its ability in protection against oxidative insults. While combined actions of ascorbate in regulating epigenetics and antioxidation appear to effectively prevent cancer development, pharmacological doses of ascorbate and dehydroascorbate may exert tumoricidal activity through redox-dependent mechanisms.

Ascorbic Acid Protects Bone Marrow from Oxidative Stress and Transient Elevation of Corticosterone Caused by X-ray Exposure in Akr1a-Knockout Mice

“…The results imply that SOD3 was produced by the homed cells and protected the irradiated tissues including bone marrow through the scavenging of superoxide by SOD3. Since Asc also effectively scavenges radicals including superoxide [7,8], it is thought that HSCs were protected from the cytotoxic effects of oxygen radicals by Asc in our study.…”

“…Since the replenishment of Asc leads to a decreased glucocorticoid response in humans and in animal models after exposure to a psychological or physical stressors [50], Asc likely acts to suppress the injurious effects of the glucocorticoid that is released under stress conditions. Because Asc is a potent antioxidant, scavenging oxygen radicals with electron donation [7,8], the primary action of Asc appears to be that of protecting BMCs against ROS that are produced by ionizing radiation and by corticosterone response. Since Asc exerts pleiotropic functions, it is also possible that Asc stimulates the hematopoietic process by supporting enzymatic reactions, such as prolyl hydroxylase, or by epigenetically regulating gene expression [51].…”

“…Compounds that exhibit antioxidant activity are promising agents that tend to reduce oxidative damage to BMCs. Ascorbic acid (Asc) is condensed in some cellular organelles and is considered to be one of the strongest forms of antioxidants among nutritional Antioxidants 2024, 13, 152 2 of 14 compounds [7,8]. In fact, many studies have established the beneficial action of Asc in protecting cells from unfavorable reactions caused by exposure to X-rays [9][10][11][12].…”

Intravenous Vitamin C Supplementation in Allogeneic Hematopoietic Cell Transplant Recipients: Salutary Impact on Clinical Outcomes

“…11 18 19 Given this logic the clinical trial reported here was designed to rapidly restore vitamin C following transplantation and utilize its endothelial stabilizing effect to reduce the impact of mucosal and endothelial injury post-transplant. 20 21 Ameliorating the tissue injury in turn would modulate the inflammatory milieu, potentially mitigating alloantigen presentation in the early days following transplant, eventually reducing GVHD likelihood evolving from recovering donor derived T cells. This concept is supported here by the observed trend toward reduced acute GVHD (grade II-IV) and chronic GVHD in Vitamin C recipients, as visualized in the graph analysis.…”

Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease

“…Ascorbate (vitamin C) is an essential micronutrient in primates and serves as an antioxidant and a cofactor for various enzymatic activities represented by prolyl hydroxylases ( Fujii et al, 2022 ). Because the induction of glycolysis by mTOR is mediated by the activation of HIF1-α and stimulation of glycolytic enzymes and ascorbate inhibits HIF-1α expression, it inhibits training immune in a dose-dependent manner ( Cheng et al, 2014 ).…”