Vitamin C protects against ionizing radiation damage to goblet cells of the ileum in rats
Introduction
In organisms exposed to long-term ionizing radiation for acute and chronic diseases, accompanying tissue and cell damage may develop, depending on the dose and exposure time (Weiss et al., 1990). More than half of all cancer patients receive radiation therapy at some period during the course of their disease. However, radiation therapy of cancer continues to be dose-limited by the tolerance of critical surrounding normal tissues.
The intestine is an important dose-limiting organ during radiation therapy of tumors in the pelvis or abdomen. Intestinal radiation toxicity (radiation enteropathy) is, by convention, classified as early or delayed, depending on when it occurs relative to the time of radiation therapy (Wang et al., 2006). It was previously believed that the severity of intestinal radiation toxicity depended directly on cell death in intestinal crypts. This view has been supplanted by the recognition that radiation-induced changes in cellular function and alterations secondary to cell death contribute substantially to the intestinal radiation response (Denham et al., 2001; Denham and Hauer-Jensen, 2002). Because these functional and secondary changes develop over time after radiation exposure, they are particularly promising targets for interventions aimed at preventing or reducing intestinal radiation toxicity.
The gastrointestinal tract is covered by a mucous layer secreted by goblet cells, which arise from pluripotent stem cells present at the base of crypts (Cheng and Leblond, 1974). Goblet cells reside throughout the length of the intestine and are responsible for the production and maintenance of the protective mucous blanket by synthesizing and secreting high molecular weight mucins (Cheng, 1974; Cheng and Leblond, 1974; Forstner, 1978). Other components within the mucus gel include water, electrolytes, sloughed epithelial cells and secreted immunoglobulins. This produces a physical and chemical barrier that protects the epithelium from physical damage by luminal contents, guards against bacterial invasion, regulates epithelial hydration and interacts with secreted immunoglobulin A to produce antibody and antitoxin effects. Much is known about the biochemical nature of mucins and the qualitative distribution of goblet cells in the small intestine (Kemper and Specian, 1991; Specian and Oliver, 1991). However, a kinetic analysis of goblet cell dynamics of rat small intestine in the process of restitution of surface epithelium subjected to radiation injury has to our knowledge not so far been reported.
The effects of radiation are caused mainly by the generation of reactive oxygen species (ROS). These ROS interact with biological molecules producing toxic free radicals leading to lipid peroxidation and DNA damage (Jagetia and Reddy, 2005). Lipid peroxidation has important effects on biological membranes and studies on lipid peroxidation can provide important information about detrimental effects of gamma-radiation. Apart from the lipid peroxidation, ROS can also alter the balance of endogenous protective systems, such as glutathione and enzymic antioxidant (SOD, CAT and GPx) defence systems (Prasad et al., 2005). The endogenous antioxidant defences are inadequate to reduce the radiation-induced free radicals. Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Several dietary antioxidants have been reported to decrease free radical attack on biomolecules (El-Habit et al., 2000). Numerous studies have examined the radioprotective effects of antioxidant free radical scavengers, which protect the cell and its organic constituent molecules from free radical damage.
Vitamin C (ascorbic acid) has been reported to be an effective antioxidant and free radical scavenger and, in vivo and in vitro conditions, reduce oxidative and free radical-induced damage to DNA and membranes in biological systems (Wilson, 1983). Vitamin C functions as a free radical scavenger of active and stable oxygen radicals and has been shown to protect several biological systems against ionizing radiation. The radioprotective effect of ascorbic acid seems to be due to its interactions with radiation-induced free radicals (Duschesne et al., 1975). Ascorbic acid pre-treatment inhibited the radiation-induced elevation in lipid peroxidation (Jagetia, 2004). It protected the mice against radiation-induced sickness, reduced the mortality and improved the healing of wounds after exposure to whole body gamma-radiation (Mallikarjun Rao and Jagetia, 2004).
Radioprotective effects of vitamin C have been restricted to pro-oxidant properties in high doses. No study has been reported so far on the radioprotective activity of vitamin C on ileum goblet cells. The aim of the present study was to evaluate the radioprotective effect of vitamin C on gamma-radiation-induced damage to ileum goblet cells.
Section snippets
Animals
Thirty male Wistar albino rats weighing between 250 and 300 g were randomized into the following study groups: I control; II, single dose radiation treated; III, two dose radiation treated; IV, single dose radiation treated with vitamin C; V, two dose radiation treated with vitamin C. Each group contained six animals. All animals were kept under standardized conditions: temperature between 22 and 24 °C, relative humidity 50–60%, and 12 h light:dark cycle. They were fed a standard laboratory diet
Histology
Single and two dose radiation caused mucosal injury. Four days after irradiation, the tips of the villi were denuded, villous tips covered by goblet cells were observed, and villous height was diminished (Figure 1; B1-B2, C1-C2). Concomitant with cell depletion, additional alterations in cell morphology were observed in the epithelium. The atrophic mucosa was lined with a continuous layer of grossly abnormal racket-shaped epithelial cells at the luminal side of the ileum. The epithelial cell
Discussion
The results of the present study indicate that treatment with vitamin C may protect ileal goblet cells from the damaging effects of ionizing radiation as determined using histological and ultrastructural indices. The degree of radiation-induced cell damage depends on several factors including the radiation dose, stage of the cell within the cell cycle, levels of cellular antioxidant defence, time of administration and the availability of oxygen in tissues during irradiation (Weichselbaum et
Acknowledgments
This study was supported as Project 633 by Trakya University Research Center, Edirne, Turkey. The authors would like to thank Associate Professor Doctor Mustafa Cem Uzal and M.Sc. Fadime Alkaya for irradiation studies.
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