Radioprotective potential of Lagenaria siceraria extract against radiation-induced gastrointestinal injury.

The cucurbits (prebiotics) were investigated as novel agents for radio-modification against gastrointestinal injury. The cell-cycle fractions and DNA damage were monitored in HCT-15 cells. A cucurbit extract was added to culture medium 2 h before irradiation (6 Gy) and was substituted by fresh medium at 4 h post-irradiation. The whole extract of the fruits of Lagenaria siceraria, Luffa cylindrica, or Cucurbita pepo extract enhanced G2 fractions (42%, 34%, and 37%, respectively) as compared with control (20%) and irradiated control (31%). With cucurbits, the comet tail length remained shorter (L. siceraria, 28 µm; L. cylindrica, 34.2 µm; C. pepo, 36.75 µm) than irradiated control (41.75 µm). For in vivo studies, L. siceraria extract (2 mg/kg body weight) was administered orally to mice at 2 h before and 4 and 24 h after whole-body irradiation (10 Gy). L. siceraria treatment restored the glutathione contents to 48.8 µmol/gm as compared with control (27.6 µmol/gm) and irradiated control (19.6 µmol/gm). Irradiation reduced the villi height from 379 to 350 µm and width from 54 to 27 µm. L. siceraria administration countered the radiation effects (length, 366 µm; width, 30 µm, respectively) and improved the villi morphology and tight junction integrity. This study reveals the therapeutic potential of cucurbits against radiation-induced gastrointestinal injury.

Dietary Pectin Increases Intestinal Crypt Stem Cell Survival following Radiation Injury.

Gastrointestinal (GI) mucosal damage is a devastating adverse effect of radiation therapy. We have recently reported that expression of Dclk1, a Tuft cell and tumor stem cell (TSC) marker, 24h after high dose total-body gamma-IR (TBI) can be used as a surrogate marker for crypt survival. Dietary pectin has been demonstrated to possess chemopreventive properties, whereas its radioprotective property has not been studied. The aim of this study was to determine the effects of dietary pectin on ionizing radiation (IR)-induced intestinal stem cell (ISC) deletion, crypt and overall survival following lethal TBI. C57BL/6 mice received a 6% pectin diet and 0.5% pectin drinking water (pre-IR mice received pectin one week before TBI until death; post-IR mice received pectin after TBI until death). Animals were exposed to TBI (14 Gy) and euthanized at 24 and 84h post-IR to assess ISC deletion and crypt survival respectively. Animals were also subjected to overall survival studies following TBI. In pre-IR treatment group, we observed a three-fold increase in ISC/crypt survival, a two-fold increase in Dclk1+ stem cells, increased overall survival (median 10d vs. 7d), and increased expression of Dclk1, Msi1, Lgr5, Bmi1, and Notch1 (in small intestine) post-TBI in pectin treated mice compared to controls. We also observed increased survival of mice treated with pectin (post-IR) compared to controls. Dietary pectin is a radioprotective agent; prevents IR-induced deletion of potential reserve ISCs; facilitates crypt regeneration; and ultimately promotes overall survival. Given the anti-cancer activity of pectin, our data support a potential role for dietary pectin as an agent that can be administered to patients receiving radiation therapy to protect against radiation-induces mucositis.

Effects of alpha-lipoic acid on associative and spatial memory of sham-irradiated and 56Fe-irradiated C57BL/6J male mice.

Cranial irradiation with (56)Fe, a form of space radiation, causes hippocampus-dependent cognitive changes. (56)Fe irradiation also increases reactive oxygen species (ROS) levels, which may contribute to these changes. Therefore, we investigated the effects of the antioxidant alpha lipoic acid (ALA) on cognition following sham-irradiation and irradiation. Male mice were irradiated (brain only) with (56)Fe (3 Gy) or sham-irradiated at 6-9 months of age. Half of the mice remained fed a regular chow and the other half of the mice were fed a caloric-matched diet containing ALA starting two-weeks prior to irradiation and throughout cognitive testing. Following cognitive testing, levels of 3-nitrotyrosine (3NT), a marker of oxidative protein stress, and levels of microtubule-associated protein (MAP-2), a dendritic protein important for cognition, were assessed using immunohistochemistry and confocal microscopy. ALA prevented radiation-induced impairments in spatial memory retention in the hippocampal and cortical dependent water maze probe trials following reversal learning. However, in sham-irradiated mice, ALA treatment impaired cortical-dependent novel object recognition and amygdala-dependent cued fear conditioning. There was a trend towards lower 3NT levels in irradiated mice receiving a diet containing ALA than irradiated mice receiving a regular diet. In the hippocampal dentate gyrus of mice on regular diet, irradiated mice had higher levels of MAP-2 immunoreactivity than sham-irradiated mice. Thus, ALA might have differential effects on the brain under normal physiological conditions and those involving environmental challenges such as cranial irradiation.

Study on the effects of Guiqi Oral Liquid in promoting recovery of hematopoiesis in acute irradiation injured mice.

OBJECTIVE: To explore the effects and possible mechanisms of Guiqi Oral Liquid (GQOL) on the recovery of hematopoiesis in acute irradiation injured mice. METHODS: The acute irradiation injured mice were randomly divided into 2 groups: the treated group and the control group, and also a normal control group was set up with 6 mice in it receiving no treatment. After the mice in the former two groups were irradiated by 6.0 Gy (60)Co gamma-ray, every one of them was given 0.4 ml GQOL or saline in equal volume through a gastric tube twice a day for 14 days. On the 4th, 8th and 14th day after irradiation, the bone marrow mononuclear cells (BMMNC) and megakaryocytes in bone marrow tissues of the mice were counted, the proportion of hematopoietic tissues (by area) was measured, and the expression of adhesion molecules, CD44 and CD54, in bone marrow were estimated by immunochemistry. The colony forming unit of spleen (CFU-S) in the mice were counted on the 8th day after irradiation. RESULTS: On the 4th, 8th, 14th day after irradiation, the count of BMMNC and megakaryocyte, and the proportion of hematopoietic tissues in the treated group were higher than those in the control group (P < 0.01 or P < 0.05). CD44 and CD54 expression in the treated group were higher than those in the control group on the 4th and 8th day (P < 0.01), but near normal on the 14th day (P < 0.01). On the 8th day, CFU-S count in the treated group was higher than that in the control group (P < 0.01). CONCLUSION: GQOL can regulate the expression of adhesion molecules, CD44 and CD54, in the bone marrow of the acute irradiation injured mice, which may be one of the mechanisms of GQOL in accelerating the early phase hematopoiesis recovery of mice.

Dietary sugar beet fiber ameliorates diarrhea as an acute gamma-radiation injury in rats.

Gamma radiation induces diarrhea as an acute injury. We have studied whether ingestion of sugar beet fiber influences radiation-induced diarrhea. Abdominal irradiation with gamma rays induced diarrhea in male Wistar/ST rats from 2 to 7 days after a single sublethal dose. The body weight of the irradiated rats was decreased temporarily at 4 days after irradiation regardless of the ingestion of sugar beet fiber. At day 8, it returned to almost the same level as that of unirradiated rats. A change in daily food intake resulted in a pattern similar to that for body weight. Dietary sugar beet fiber had little significant effect on the changes in body weight and daily food intake, and its ingestion significantly decreased gamma-ray-induced diarrhea. Changes in biochemical and histological parameters in intestinal mucosa (small intestine, cecum and colon) were not greatly influenced by the ingestion of sugar beet fiber through the periods of diarrhea. It was concluded that dietary sugar beet fiber ameliorated the diarrhea induced by abdominal irradiation. We suggest that the inhibitory effect of the ingestion of sugar beet fiber is due to its effects on the luminal environment, such as support for bacterial function in the luminal contents in the colon of animals that ingest sugar beet fiber.

The prophylactic and therapeutic effects of glutamine- and arginine-enriched diets on radiation-induced enteritis in rats.

BACKGROUND: Recent studies indicated that glutamine and arginine support the mucosal barrier in several ways. This experimental study hypothesized that administration of glutamine- and arginine-enriched diets before abdominal radiation therapy would provide a radioprotective effect on intestinal mucosa, and this would augment the therapeutic effectiveness provided by postirradiation administration. MATERIALS AND METHODS: A rat model of radiation enteritis was designed with a single dose of 1100 cGy to the abdomen. Thirty-five rats were randomized into five groups of seven. A 7-day glutamine-enriched diet for Group I and a 7-day arginine-enriched diet for Group II were administered both pre- and postradiation. For Groups III and IV, the same glutamine and arginine diets were given, respectively, postradiation only. Group V was fed a glutamine- and arginine-free diet and was the control group. The rats underwent laparotomy for culture of mesenteric lymph nodes and removal of segments of ileum, jejenum, and colon for microscopic examination. RESULTS: Bacterial translocation was significantly higher in Group V (P < 0.05), while intestinal villus count and villus height were significantly higher in all of the groups fed glutamine and arginine when compared with the control group (P < 0.0001 and P < 0.05, respectively). CONCLUSION: Both arginine- and glutamine-enriched diets have protective effects on gut mucosa in the postirradiation state; however, pre- and postirradiation administration together does not provide superior protection versus postradiation administration alone.

Protective effect of enriched diet plus growth hormone administration on radiation-induced intestinal injury and on its evolutionary pattern in the rat.

Adequate nutritional support can enhance the protective action of growth hormone in radiation-induced mucositis. Our aim is to address the evolutionary pattern of radiation injury to the small intestine of rats fed a high-protein diet and treated with growth hormone before irradiation. Male Wistar rats were fed a high-protein diet and killed two, four or seven days after irradiation. Animals were given either growth hormone or saline. The combination of growth hormone and high-protein diet reduced mortality, increased mucosal height and crypt proliferation, and reduced apoptosis from day 2 to day 7 after irradiation. Bacterial translocation was increased in rats fed the high-protein formula. Insulin-like growth factor was reduced by radiation and further reduced by the high-protein diet. The combination of growth hormone and high-protein diet protects from the damage caused by radiation to the bowel and accelerates its recovery. This effect does not seem to be mediated through insulin-like growth factor levels.

[Methodological principles for using agents for the mass prevention of the sequelae of human irradiation]. / Metodologicheskie printsipy primeneniia sredstv massovoi profilaktiki posledstvii oblucheniia cheloveka.

The means of mass prevention of radiation consequences are biologically active additives to food, usual diet components, etc., micronutrients, as well as some sorbents and radio protective agents, which show various actions: 1) those reducing absorption; 2) those accelerating radionuclide excretion; 3) those enhancing the body's resistance to radiation; 4) those contributing to the prevention (less risk) of late radiation-induced cancer. The paper formulates basic requirements for means of mass prevention and guidelines for their use in terms of benefits and risk.

[Food fibers--blockers and decontaminants of the radionuclides cesium and strontium]. / Pishchevye volokna--blokatory i dekorporanty radionuklidov tseziia i strontsiia.

The Chernobyl accident and its resultant radioactive pollution of enormous areas led to long-term entrance of radionuclides into the human habitat. Among more than 200 radionuclides, the products of uranium fission in the reactor of the atomic power station, the isotopes of iodine, cesium, and strontium present the highest hazard. If iodine-131 virtually decayed by August, 1986, the long-lived isotopes of cesium and strontium will still stir the world public and scientists for many years. The authors' result show that new types of dietary cellulose and composite food additives based on alfalfa polymers have rather pronounced antiradioactive properties against Cs-137 and Sr-85. This makes it necessary to organize the manufacture of these food additives whose daily dose of 12-20 should be supplemented into human diet every day.

[The dietary correction of the permeability of the protective intestinal barrier in rats after gamma irradiation]. / Korrektsiia dietoi pronitsaemosti zashchitnogo bar'era kishki krys pri gamma-obluchenii.

400 to 700 rad irradiation with gamma-rays significantly increased the intestinal permeability for ovalbumin and polyethylene glycol in rats. Consumption of cow's milk with a protein concentrate for 14 days prior to irradiation helped to normalise the disturbed permeability. The findings suggest the possibility of prophylactic use of milk for risk group subjects with acute or chronic radiation injuries.

[Comparative evaluation of radiation protective efficiency of regimens with various content of calcium, potassium and iron]. / Sravnitelnaia otsenka radioprotektornoi éffectivnosti ratsionov s razlichnym soderzhaniem kaltsiia, kaliia i zheleza.

Calcium deficit in ration of rats considerable reduced radioprotective potential of animals. The enrichment of ration for calcium, potassium, and iron improved radioprotection by changing velocity of accumulation and excretion of cesium.

[Alimentary methods for decreasing the radiation load of the body with cesium and strontium radionuclides]. / Alimentarnye sredstva umensheniia luchevykh nagruzok organizma radionuklidami tseziia i strontsiia.

Introduction in ration of fish mass, calcium carbonate, bone meal, algae laminaria reduced level of Sr-90 and Cs-137 accumulation in the population living on territories polluted after Chernobyl accident

Dietary enhancement of intestinal radioresistance during fractionated irradiation.

Rats fed laboratory chow or elemental diet 3 were given fractions of 240 rads of 60Co gamma-radiation abdominally (1200 rads/week) until all animals had died. Changes in appetite, body weight, and mortality were monitored as a function of the cumulative dose received. More radiation was needed in the diet-fed group to achieve both 0 and 100% mortality, a difference of 37% at the mean lethal dose level. Both groups developed similar progressive anorexia but the diet-fed animals lost weight more slowly. Data indicate that basic intestinal radio-resistance is enhanced by feeding the elemental diet.