Wound Healing by Ascorbic Acid in Mice
Hemi-body irradiation in multiple fractionated doses is frequently used alone or in combination with surgery for the treatment of cancer. It produces both acute and late effects on the skin that have profound effects on surgical wounds. Because of the crucial practical importance of radiation exposure associated with skin wounds, it is imperative to investigate the efficacy of cost-effective nutritional factors in the reconstruction of irradiated wounds. Therefore, the effect of ascorbic acid treatment was studied on the healing of excision wounds in mice exposed to 2, 4, 6, or 8 Gy hemi-body gamma radiation. A full-thickness skin wound was created on the dorsum of 8- to 10-week-old Swiss albino mice after hemi-body exposure to 2, 4, 6, or 8 Gy. The progression of wound contraction was monitored periodically by capturing video images of wounds. Collagen, hexosamine, deoxyribonucleic acid (DNA), nitric oxide (NO), and histological profiles of excision wounds were also evaluated and either treated or not treated with ascorbic acid before exposure to 0 or 6 Gy. Irradiation caused a dose-dependent delay in wound contraction and wound healing time, while ascorbic acid pretreatment resulted in a significant elevation in the rate of wound contraction and a decrease in mean wound healing time. Treatment with ascorbic acid before irradiation enhanced the synthesis of collagen, hexosamine, DNA, and NO, while histological assessment revealed an improved collagen deposition and an increase in fibroblast and vascular densities. The present study demonstrates that ascorbic acid pretreatment has a beneficial effect on irradiated wounds and could be part of a strategy to ameliorate radiation-induced delay in wound repair.

Acute radiation exposure is of interest to defense and civil administrations concerned about atomic weapons. However, it is also of concern to radiation safety personnel due to the possibility of accidents involving large doses of radiation, and to radiotherapists performing more localized hemi-body irradiation for cancer treatment. Hemi-body irradiation in multiple fractionated doses is frequently used alone or in combination with surgery or other modalities for the treatment of various solid tumors. It produces both acute and late effects on the skin and subcutaneous tissues that have profound effects on the healing of surgical wounds. Interaction of ionizing radiation with wounded tissue will create a situation where normal response to injury will be disrupted, leading to a protracted recovery period. Irradiation has been reported to produce multiple negative effects on wound healing processes: it inhibits inflammatory reactions, connective tissue proliferation, tissue formation, maturation of granulation tissue, transcription of collagen mRNAs, secretion of collagen, and neovascularization. Skin wounds after irradiation may be complicated by infections encouraged by bone marrow injury. Fibroblasts in irradiated tissue either have decreased ability to replicate or there is a selective ablation of faster growing fibroblasts by irradiation.

Successful healing of wounds represents the sum of a sequence of well organized basic processes including inflammation, cell proliferation, matrix formation, remodeling, wound contraction, and epithelization. Interaction of ionizing radiation with the normal wound healing process leads to delayed healing or chronic nonhealing wounds. An adequate knowledge of the altered pathophysiology of irradiated wounds is necessary to make a proper judgement to select potential therapeutic modalities and prophylaxis for irradiated wounds. Several attempts have been made to identify potential therapeutic approaches to augment healing in this setting. Hydrogel and hydrocolloid gel dressings have been used to decrease wound discomfort and wound healing time in radiation ulcers. Phenytoin sodium has been reported to enhance the stimulating action of wound fluid on proliferation of fibroblasts and synthesis of collagen after irradiation. There is evidence that supplemental vitamin A prevents the acute radiation-induced defects in wound healing, probably by enhancing the early inflammatory reaction to the wound and increasing the number of monocytes and macrophages at the wound site. Certain radioprotective compounds like mercaptoethylamine, serotonin, and WR2721 (amifostine) have also been found to be useful in combined injuries. Several growth factors and antimicrobial agents have been explored in animal models as potential options to improve wound healing in radiation-damaged skin.

Although basic research has suggested many potential therapies and prophylaxis for irradiated wounds, little attention has been given to the effects of dietary ingredients on the radiation response of healing wounds, which emphasizes a need for continued research in the area of medical management of irradiated wounds. Since wound healing abnormalities cause great physical and psychological stress to affected patients and are extremely expensive, the use of nutritional factors in the reconstruction of irradiated wounds is an attractive proposition because they have wide acceptability, better tolerance, do not have side effects, and can be safely manipulated for human use. Ascorbic acid is an essential ingredient of the daily human diet, and its supplementation has been proven to promote wound healing in animals and humans. Ascorbic acid treatment has also been reported to confer protection against radiation in vitro and in vivo and has beneficial effect on the course of radiation-induced skin injuries. The present study was undertaken to investigate the efficacy of ascorbic acid treatment in mice exposed to different doses of hemi-body gamma radiation and stressed with additional trauma of open excision wounds on the skin.