Gamma-tocopherol supplementation ameliorated hyper-inflammatory response during the early cutaneous wound healing in alloxan-induced diabetic mice

Abstract

Gamma tocopherol has shown ameliorative effect on diabetic wound healing by regulation of inflammation, oxidative stress, and apoptosis demonstrated by nuclear factor kappa B, nuclear factor (erythroid derived 2)-like 2, and sirtuin-1. AbstractDelayed wound healing is one of the major diabetic complications. During wound healing process, the early inflammatory stage is important for better prognosis. One of antioxidant nutrient, gamma-tocopherol (GT) is considered to regulate inflammatory conditions. This study investigated the effect of GT supplementation on mechanism associated with inflammation, oxidative stress, and apoptosis during early cutaneous wound healing in diabetic mice. Diabetes was induced by alloxan injection in ICR mice. All mice were divided into three groups: non-diabetic control mice (CON), diabetic control mice (DMC), and diabetic mice supplemented with GT (GT). After two weeks of GT supplementation, excisional wounds were made by biopsy punches (4 mm). Diabetic mice showed increases in fasting blood glucose (FBG) level, hyper-inflammatory response, oxidative stress, and delayed wound closure rate compared to non-diabetic mice. However, GT supplementation reduced FBG level and accelerated wound closure rate by regulation of inflammatory response-related proteins such as nuclear factor kappa B, interleukin-1b, tumor necrosis factor-a, and c-reactive protein, and oxidative stress-related markers including nuclear factor (erythroid derived 2)-like 2, NAD(P)H dehydrogenase quinone1, heme oxygenase-1, manganese superoxide dismutase, catalase and glutathione peroxidase and apoptosis-related markers such as sirtuin-1, peroxisome proliferator-activated receptor gamma coactivator 1-, and p53 in diabetic mice. Taken together, GT would be a potential therapeutic to prevent diabetes-induced delayed wound healing by regulation of inflammatory response, apoptosis, and oxidative stress.

The effects of magnesium and vitamin E co‐supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

“…The evidence suggests that magnesium acts as an important cofactor for enzymes involved in protein and collagen synthesis during the process of wound curing . In addition, vitamin E intake may improve diabetic wound healing through the regulation of apoptosis, inflammatory response and oxidative stress, enhancing mitochondrial function and increasing the gene expression of cell growth factors . Joint magnesium and vitamin E supplementation may confer more beneficial effects by adding the potential influences related to their single supplementation.…”

“…It is also necessary for the synthesis of protein and tissue development during wound curing process . Experimental studies proposed that vitamin E has been effective in supporting diabetic wound healing by the regulation of inflammatory reaction, apoptosis and antioxidant defense system . Considering the numerous beneficial effects of magnesium and vitamin E on mechanisms related to metabolic control, and wound healing process and due to the proposed additive action for the combination of these nutrients, the present study was conducted to evaluate the effects of magnesium and vitamin E co‐supplementation on wound healing, glycemic status, lipid profiles, and biomarkers of inflammation and oxidative stress in patients with DFU.…”

Wound Healing Properties of Selected Natural Products

“…or intraperitoneally (i.p.)]. Accelerated wound closure rate was detected in both genetically and chemically-induced diabetic rodents [ 51 , 52 , 53 , 54 , 55 ]. Vitamin E-related intervention facilitated the formations of new blood capillaries (angiogenesis), epithelium (epithelialization), tissue granulation, collagen fibers and dermis layers at the excisional and incisional wounds.…”

“…Overwhelming inflammatory response and ROS production exceeding the capacity of the endogenous defense may lead to tissue damage, thus suggesting the pivotal role of inflammation and ROS modulation during wounding [ 65 ]. Previous studies indicated that vitamin E regulated oxidative stress [decreased 4-hydroxynoneal (4-HNE) and malondialdehyde (MDA) levels] and inflammation [reduced nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB), TNF-α, and IL-1β] in diabetic cutaneous wounds [ 53 , 54 , 58 ]. Vitamin E also increased the anti-oxidative enzymes such as SOD, GPx and CAT responsible for detoxifying ROS and oxidized macromolecules in wound tissues [ 52 ].…”

Gc-MS Analysis of Bioactive Compounds From the Ethanol Extract of Leaves of Neibuhria Apetala Dunn.

“…For instance, gamma-tocopherol was more efficient than alpha tocopherol inhibitory prostate cancer cell expansion. This reduces oxidative DNA injury and increases superoxide dismutase activity 16 . γ tocopherol has anti inflammatory action and enhances wound healing 17 .…”