Vitamin C promotes wound healing through novel pleiotropic mechanisms

Abstract

Vitamin C (VitC) or ascorbic acid (AscA), a cofactor for collagen synthesis and a primary antioxidant, is rapidly consumed post-wounding. Parenteral VitC administration suppresses pro-inflammatory responses while promoting anti-inflammatory and pro-resolution effects in human/murine sepsis. We hypothesised that VitC could promote wound healing by altering the inflammatory, proliferative and remodelling phases of wound healing. Mice unable to synthesise VitC (Gulo(-/-) ) were used in this study. VitC was provided in the water (sufficient), withheld from another group (deficient) and supplemented by daily intra-peritoneal infusion (200 mg/kg, deficient + AscA) in a third group. Full thickness excisional wounds (6 mm) were created and tissue collected on days 7 and 14 for histology, quantitative polymerase chain reaction (qPCR) and Western blotting. Human neonatal dermal fibroblasts (HnDFs) were used to assess effects of In conclusion, VitC favorably on proliferation. Histological analysis showed improved wound matrix deposition and organisation in sufficient and deficient +AscA mice. Wounds from VitC sufficient and deficient + AscA mice had reduced expression of pro-inflammatory mediators and higher expression of wound healing mediators. Supplementation of HnDF with AscA induced the expression of self-renewal genes and promoted fibroblast proliferation. VitC favourably impacts the spatiotemporal expression of transcripts associated with early resolution of inflammation and tissue remodelling.

Role of vitamin C in wound healing after dental implant surgery in patients treated with bone grafts and patients with chronic periodontitis

“…In contrast, intravenous administration of vitamin C may have yielded plasma vitamin C concentrations approximately 250-times higher than that of patients receiving vitamin C supplements orally. 18 In this study, the effects on wound healing became visible by day 14 postsurgery. The surgical procedure conducted in patients from group D was less invasive than the procedure performed in the other groups, which suggests that group D plasma vitamin C levels may have been affected less by the surgery.…”

“…25,26 The healing process for oral wounds closely mimics the wound healing of other connective tissues in the body. 24,28 Previously, Mohammed and colleagues 18 showed that vitamin C could promote wound healing through a variety of mechanisms. 24,28 Previously, Mohammed and colleagues 18 showed that vitamin C could promote wound healing through a variety of mechanisms.…”

“…17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins. 17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins.…”

“…17,18 Vitamin C can decrease the responses of some inflammatory biomarkers, including C-reactive protein, and several pro-inflammatory cytokines such as tumor necrosis factor, interferons, and interleukins. 18 Therefore, vitamin C promotes wound healing through pleiotropic mechanisms, including promoting matrix deposition and neovascularization in healing wounds and reducing the secretion of inflammatory mediators. 18 Therefore, vitamin C promotes wound healing through pleiotropic mechanisms, including promoting matrix deposition and neovascularization in healing wounds and reducing the secretion of inflammatory mediators.…”

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

“…In addition to the vascular effects outlined above, it is well established that AA levels in the scurvy range (ie, below 10 micromolar), as in our cohort may be associated with wound healing impairment . Repletion of ascorbate in these settings, accelerates wound healing and may result in attenuation of oral and gastrointestinal mucosal injury and subsequently diminished release of inflammatory cytokines (IL‐1 and TNF‐α), with up‐regulation of mediators of wound healing (TGF‐β and vascular endothelial growth factor) in animal models . Similar effect has been demonstrated in a swine model of multiple injuries where AA administration attenuated the organ injury and with relative reduction in the production of TNF, IL‐1, IL‐8, tissue factor, and plasminogen activation inhibitor‐1 .…”