Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

Abstract

BackgroundDiabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response.MethodsDiabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet), DM (diabetic mice fed AIN 93 G purified rodent diet), VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet), and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet). After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site.ResultsDietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice.ConclusionsThese findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response.

High-Glucose Environment Enhanced Oxidative Stress and Increased Interleukin-8 Secretion From Keratinocytes

“…The results from our in vitro experiments suggest that antioxidants may reduce IL-8 expression from high glucose–cultivated keratinocytes and therefore improve diabetic wound healing via normalization of overzealous inflammatory reactions. In support of this hypothesis, a recent report has shown that supplementation of dietary antioxidants selectively regulates the inflammatory responses and promotes wound healing in diabetic mice (31). …”

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

“…34 In the current study, we investigated that GT supplementation ameliorated delayed wound healing through improvement of inflammation, oxidative stress, and apoptosis, in particular, in the early inflammatory stage of cutaneous wound healing in alloxan-induced diabetic mice. GT is a more potent anti-inflammatory substance compared to AT.…”

α‐Tocopherol promotes HaCaT keratinocyte wound repair through the regulation of polarity proteins leading to the polarized cell migration

“…α‐Toc is known to act as a potent chain‐breaking antioxidant in biomembrane systems . Supplementation of dietary antioxidants including vitamin E promoted wound healing in the patients with wound as well as diabetic mice . Furthermore, the in vitro study revealed that 200 µM α‐Toc (relatively higher concentration) enhanced wound healing of the plasma membrane of myocytes through its antioxidant activity .…”