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Aim: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid., Background: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol., Objective: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study., Methods: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon., Results and Discussion: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury., Conclusion: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Effect of tripeptide on the process of postradiational restoration of duodenum in rats has been studied in model of accelerated aging. Geroprotective effect of tripeptide was connected with reparation of bloodstream in duodenum and increase proliferative activity of duodenal epiteliocytes.

Pronounced ultrastructural changes in vessels and mast cells were observed in duodenal lamina propria of Wistar rats 1 year after single whole-body gamma-irradiation in a dose of 7.5 Gy. Inhibition of adrenocortical function with methopyrone reduced structural damage and improved animal survival.

Previous work on small intestinal radiation injury has reported changes in epithelial and non-epithelial tissues, but with few quantitative comparisons of different responses by individual cell types. The approach used here quantifies the responses of mouse duodenum to X-irradiation with 6 Gy, 10 Gy and 20 Gy, sampled three days after treatment, and 10 Gy sampled 6 hours, 1 day and 3 days after treatment. Tissue area measurements and counts per circumference for 13 different structural elements are subjected to statistical tests. New data reported here for X-irradiation include the fact that cryptal cells do not respond uniformly, indicating that the crypt/microcolony cannot always be used as a standard unit in assessing radiation injury. Non-epithelial structures, such as submucosal arterioles, are also affected. The data display also includes control-referenced ratios, from which are calculated Tissue Indices and a final Morphological Index, which estimates total structural damage. The Indices are useful in drawing attention to unexpected changes in extent or range of data sets. In addition, the Epithelial Index appears to be a sensitive indicator of radiation damage, even at low doses and early time points. The data display includes a graph of the total Indices and summary tables of data, and encourages close study of the constituent data points.

Disturbances of gastrointestinal function are an important limiting factor in radiotherapy of the abdominal and pelvic regions. The pathogenesis of radiation induced intestinal dysfunction is not completely understood, although the intestinal mucosa has been shown to respond to irradiation by a progressive reduction in villous size. Since blood vessels in other organs have been implicated in the initiation of post-irradiation changes, the present study examines the response of villous blood vessels to an X-ray dose of 10 Gy after 3 days. Vascular corrosion casts and light and transmission electron microscopy (TEM) were used to study the post-irradiation vascular response. In control and sham-irradiated animals, the villous plexus was fountain-like: an arteriole entered the villous base and divided apically into two terminal branches. Villous capillaries apparently derived from the terminal branches, and united to form venules. In capillary loops the vertical inter-capillary distance was greater than the horizontal inter-capillary distance. After irradiation, the vessels became tortuous and the plexus was compressed apico-basally, shown by a decrease in the vertical inter-capillary distance. The capillary luminal diameter, as measured on resin semi-thin sections, was significantly increased. TEM showed that the endothelium was irregular and there was evidence of plasma leakage. These results suggest that villous damage seen after irradiation can include changes in the villous vasculature.

Thirty-nine adult male Beagles received either fast neutron or photon irradiation to the right thorax to determine the relative biological effectiveness (RBE) of fast neutrons on normal pulmonary tissue. The right anterior abdomen was included in the field of radiation. Twenty-four dogs (six/group) received fast neutrons with an average energy of 15 MeV to total doses of 1000, 1500, 2250 or 3375 rad in four fractions per week for six weeks. Fifteen dogs received 3000, 4500 or 6750 rad of photons (five/group) in an identical fractionation pattern. All neutron irradiated dogs receiving 3375 and 2250 rad and one receiving 1500 rad developed clinical signs of pancreatic, hepatic and gastrointestinal disturbances. The liver enzymes of these dogs became elevated and they died or were euthanatized in extremis 47-367 days after irradiation. Only one 6750 rad photon dog developed similar signs and died 708 days post-irradiation. Five neutron and 10 photon exposed dogs died of other causes. Neutron-induced lesions in the stomach and duodenum included hemorrhages, erosions, ulcerations and fibrosis. Ulcers perforated the GI tract of five dogs. Pancreatic lesions included degranulation and necrosis of acinar cells, fibrosis ans atrophy. Islet cells were not obviously damaged. All lesions were associated with degenerative and occlusive vascular changes. The RBE of fast neutrons, assessed by clinical signs, gross and microscopic pathology, is approximately 3-4.5 for pancreas and about 4.5 for pylorus and duodenum.

The experiment was carried out on 40 rabbits divided in four groups. Each animal of the experimental groups received a 850 R dose. X-rays were applied for irradiation. The animals were sacrificed on the 7th, 12th and 17th day after irradiation. Levels of ATP/ADP and phosphocreatine were determined in the skeletal muscles, myocardium, liver, kidneys, blood and the mucosa of duodenum. On the 7th day, in all tissues a decrease of the phosphocreatine level was observed. The lowest level differed little from zero. Afterwards a slow increase of phosphocreatine concentration took place, reaching the normal level in the kidneys on the 17th day after irradiation. The concentration of ATP/ADP was the lowest on the 7th day of the experiment. A fast increase of that fraction was observed in the liver, where the level of ATP/ ADP on the 12th day was higher than in the control group. From the 12th day, a drop in the ATP/ADP level was observed, reaching the normal level on the 17th day. In the skeletal and heart muscles, after a drop on the 7th day, a slow increase of the activity was observed on the last day of the experiment, but the activity did not reach the normal level.

The effect of postradiation bleeding on the dynamics of duodenal crypts' cells proliferation in rats was studied. The animals, females, three months old, weighing 170 or 180 g, were exposed to radiation of 800 R (115 R/min) and immediately after irradiation were bled by cardiac puncture to 50% of total blood volume. Proliferative activity of duodenal epithelium cells was monitored for a period of five days after irradiation. For control purposes normal, irradiated and only bled animals were used. The results demonstrated that although there are no significant differences in proliferative activity of duodenal epithelium cells in irradiated and bled animals and only irradiated animals, the postradiation reparative processes in irradiated and bled animals is considerably more stable. It is considered that bleeding itself by its hypoxic activity reduced the sensitivity of epithelium to the dose of radiation used. On the other hand, bleeding removed the damaging agents which appear after total body irradiation.

Twenty four rabbits were used in the experiment. The animals were divided into four groups, 6 animals in each. The rabbits were irradiated with a total dose of 910 R. The activity of alkaline phosphatase and the level of inorganic phosphorus were measured on the 5th, 10th and 15th day after irradiation in erythrocytes, plasma, duodenum, muscles and liver. There was found a decrease of phosphatase activity in the plasma, liver and duodenum, and an increase in the muscles and erythrocytes. The level of inorganic phosphorus increased in the duodenum, liver and plasma, and decreased in the muscles and erythrocytes. In the latter two, the increase of the phosphatase activity was accompanied by a decrease of the phosphorus level; on the contrary, the decrease of the enzyme activity in the liver and duodenum was accompanied by an increase of the phosphorus level. During the whole experimental period, the phosphatase activity was higher by about 40% than in the control group.

Functional changes in the intestinal responsiveness to a fixed dose of acetylcholine were studied in muscle strips removed from young adult male rats previously exposed to whole body gamma radiation. In the irradiated rat the responsiveness to a fixed dose of acetylcholine was found to be augmented in the small intestine but not in the colon. Similar motor patterns for the small intestine were found when muscle strips from adrenalectomized rats were studied. Preradiation adrenalectomy further exaggerated the post-radiation sensitivity of the rat small intestine to acetylcholine. Hypophysectomy prior to either adrenalectomy and/or whole body radiation was associated with an absence of augmented small intestinal motor activity following administration of acetylcholine. The response of the large bowel to acetylcholine, however, was not modified by adrenalectomy and/or hypophysectomy. These observations suggest an endocrine component to the acute 3--5 day intestinal radiation syndrome.

Thoracic irradiation induced duodenal lesions in mice as an indirect effect. We studied the influence of partial thoracic irradiation on endogenous histamine stores in the alimentary canal. Mice subjected to lower mediastinal irradiation had significantly higher (+19%) median gastric histamine, but lower (-44%) distal duodenal histamine than controls. They also had significantly lower proximal (-39%) and distal (-44%) duodenal histamine than mice who received upper mediastinal irradiation. Twenty-three percent of mice after lower mediastinal irradiation had duodenal lesions; these had significantly lower proximal (-30%) and distal (-44%) duodenal histamine than controls. Thus, irradiation to the lower mediastinum induced both duodenal lesions and significant changes in gastric and duodenal histamine stores. Histamine may be involved in the pathogenesis of these lesions.

Electron microscopy has revealed death of some of the apudocytes and recovery of the other ones in small intestine of rats after single total body irradiation in sublethal dose (5 Gy) and local fractionated irradiation (35 Gy, 7 Gy X 5) of the abdomen. The ability of EC-cells to form the autophagosomes was found. An absence of uniform reaction of different types of apudocytes to radiation is discussed.