The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage.

PURPOSE: We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS: Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS: RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS: We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.

Astragalus polysaccharide has a protective effect on hematopoiesis in an irradiated mouse model and decreases apoptosis in megakaryocytes.

Huangqi, the dried root of Radix Astragali, is an essential herb in Traditional Chinese Medicine and has been used to promote hematopoiesis for centuries. Astragalus polysaccharide (ASPS), the bioactive compound of Huangqi, serves a crucial role in hematopoiesis. The aim of the present study was to investigate the hematopoietic effects, in particular the thrombopoietic effects, and the molecular mechanisms of ASPS using an irradiation­induced myelosuppressive mouse model. Colony­forming unit assays, flow cytometric analysis of apoptosis, ELISAs, Giemsa staining and western blotting were performed to determine the hematopoietic and anti­apoptotic effects of ASPS. The results demonstrated that ASPS enhanced the recovery of red blood cells at day 21 following treatment, as well as platelets and white blood cells at day 14. In addition, ASPS promoted colony formation in all lineages (megakaryocytes, granulocyte monocytes, erythroid cells and fibroblasts). The morphological study of the bone marrow demonstrated that tri­lineage hematopoiesis was preserved in the ASPS­ and thrombopoietin (TPO)­treated groups compared with the control group. The overall cellularity (mean total cell count/area) of the ASPS­treated group was similar to that of the TPO­treated group. Additionally, in vitro experiments indicated that treatment with 100 µg/ml ASPS exhibited the maximum effect on colony formation. ASPS attenuated cell apoptosis in megakaryocytic cells via inhibiting the mitochondrial caspase­3 signaling pathway. In conclusion, ASPS promoted hematopoiesis in irradiated myelosuppressive mice possibly via enhancing hematopoietic stem/progenitor cell proliferation and inhibiting megakaryocytes apoptosis.

Protective Effect of Selenium-L-methionine on Radiation-induced Acute Pneumonitis and Lung Fibrosis in Rat.

BACKGROUND: In this study, we aimed to detect the changes in the level of interleukin (IL)-4 and IL-13 cytokines and their downstream genes including interleukin-13 receptor subunit alpha-2 (IL13Ra2), interleukin-4 receptor subunit alpha-1 (IL4Ra1), dual oxidase 1 (DUOX1) and dual oxidase 2 (DUOX2). The protective effects of Selenium-L-methionine on radiation-induced histopathological damages and changes in the level of these cytokines and genes were detected. METHODS: Four groups of 20 rats (5 rats in each) namely, control; Selenium-L-methionine, radiation and radiation plus Selenium-L-methionine were used in this study. 4 mg/kg of Selenium-Lmethionine was administered 1 day before irradiation and five consecutive days after irradiation. Irradiation was done using a dose of 15 Gy 60Co gamma rays at 109 cGy/min. All rats were sacrificed 10 weeks after irradiation for detecting changes in IL-4 and IL-13 cytokines, the expressions of IL13Ra2, IL4Ra1, Duox1 and Duox2 and histopathological changes. RESULTS: The level of IL-4 but not IL-13 increased after irradiation. This was associated with increased expression of IL4Ra1, Duox1 and Duox2, in addition to changes in morphological properties. Selenium-L-methionine could attenuate all injury markers following lung irradiation. CONCLUSION: Selenium-L-methionine can protect lung tissues against toxic effects of ionizing radiation. It is possible that the modulation of immune responses and redox interactions are involved in the radioprotective effect of this agent.

Wuzi Yanzong pill, a Chinese polyherbal formula, alleviates testicular damage in mice induced by ionizing radiation.

BACKGROUND: Chinese medicine Wuzi Yanzong pill (WZYZP) was firstly documented in ancient Chinese medical works "She Sheng Zhong Miao Fang" by Shi-Che Zhang in 1550 AD. The traditional herbal formula is widely used in treating nephrasthenia lumbago, prospermia, erectile dysfunction and male sterility. The present study was to explore the effects of WZYZP on ionizing irradiation-induced testicular damage in mice. METHODS: The pelvic region of male mice was exposed to X-rays for inducing testicular damage. The effects of WZYZP on testicular damage were evaluated in terms of testes weight, sperm quantity and motility, testes oxidative status and serum hormone levels. The alterations in testicular structure were examined by hematoxylin-eosin staining. Additionally, changes in proliferating cell nuclear antigen (PCNA) expression of testes were explored by western blot. RESULTS: Pelvic exposure to x-ray induced reduction in testes weight and sperm quality, along with oxidative stress and abnormal testicular architecture in testes. Oral administration of WZYZP for 3 weeks markedly increased testes weight, sperm quantity and motility, and attenuated testicular architecture damage. Meanwhile, WZYZP treatment significantly reversed the reduction of serum testosterone, and decreased testes malondialdehyde (MDA) and Oxidative stress index (OSI) relative to the radiated mice. Additionally, WZYZP effectively prevented the downregulation of PCNA expression in testes induced by x-ray irradiation. CONCLUSION: These findings suggest WZYZP exhibits ameliorating effects against ionizing irradiation-induced testicular damage in mice, which may be related to its antioxidation.

The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer.

BACKGROUND: Silibinin has been known for its role in anti-cancer and radio-protective effect. Radiation therapy for treating lung cancer might lead to late-phase pulmonary inflammation and fibrosis. Thus, this study aimed to investigate the effects of silibinin in radiation-induced lung injury with a mouse model. METHODS: In this study, we examined the ability of silibinin to mitigate lung injury in, and improve survival of, C57BL/6 mice given 13 Gy thoracic irradiation and silibinin treatments orally at 100 mg/kg/day for seven days after irradiation. In addition, Lewis lung cancer (LLC) cells were injected intravenously in C57BL/6 mice to generate lung tumor nodules. Lung tumor-bearing mice were treated with lung radiation therapy at 13 Gy and with silibinin at a dose of 100 mg/day for seven days after irradiation. RESULTS: Silibinin was shown to increase mouse survival, to ameliorate radiation-induced hemorrhage, inflammation and fibrosis in lung tissue, to reduce the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and to reduce inflammatory cell infiltration in the respiratory tract. In LLC tumor injected mice, lung tissue from mice treated with both radiation and silibinin showed no differences compared to lung tissue from mice treated with radiation alone. CONCLUSIONS: Silibinin treatment mitigated the radiation-induced lung injury possibly by reducing inflammation and fibrosis, which might be related with the improved survival rate. Silibinin might be a useful agent for lung cancer patients as a non-toxic complementary approach to alleviate the side effects by thorax irradiation.

Ciprofloxacin Therapy Results in Mitigation of ATP Loss after Irradiation Combined with Wound Trauma: Preservation of Pyruvate Dehydrogenase and Inhibition of Pyruvate Dehydrogenase Kinase 1.

Ionizing radiation exposure combined with wound injury increases animal mortalities than ionizing radiation exposure alone. Ciprofloxacin (CIP) is in the fluroquinolone family of synthetic antibiotic that are available from the strategic national stockpile for emergency use and is known to inhibit bacterial sepsis. The purpose of this study was to evaluate the efficacy of ciprofloxacin as a countermeasure to combined injury mortality and determine the signaling proteins involved in energy machinery. B6D2F1/J female mice were randomly assigned to receive either 9.75 Gy irradiation with Co-60 gamma rays followed by skin wounding (combined injury; CI) or sham procedure (sham). Either ciprofloxacin (90 mg/kg/day) or vehicle (VEH) (water) was administered orally to these mice 2 h after wounding and thereafter daily for 10 days. Determination of tissue adenosine triphosphate (ATP) was conducted, and immunoblotting for signaling proteins involved in ATP machinery was performed. Combined injury resulted in 60% survival after 10 days compared to 100% survival in the sham group. Furthermore, combined injury caused significant reductions of ATP concentrations in ileum, pancreas, brain, spleen, kidney and lung (-25% to -95%) compared to the sham group. Ciprofloxacin administration after combined injury resulted in 100% survival and inhibited reductions in ileum and kidney ATP production. Ileum protein levels of heat-shock protein 70 kDa (HSP-70, a chaperone protein involved in ATP synthesis) and pyruvate dehydrogenase (PDH, an enzyme complex crucial to conversion of pyruvate to acetyl CoA for entrance into TCA cycle) were significantly lower in the CI group (vs. sham group). Using immunoprecipitation and immunoblotting, HSP-70-PDH complex was found to be present in the ileum tissue of CI mice treated with ciprofloxacin. Furthermore, phosphorylation of serine residues of PDH resulting in inactivating PDH enzymatic activity, which occurred after combined injury, was inhibited with ciprofloxacin treatment, thus enabling PDH to increase ATP production. Increased ileum levels of pyruvate dehydrogenase kinase 1 protein (PDK1, an enzyme responsible for PDH phosphorylation) after combined injury were also prevented by ciprofloxacin treatment. Taken together, these data suggest that ciprofloxacin oral administration after combined injury had a role in sustained ileum ATP levels, and may have acted through preservation of PDH by HSP-70 and inhibition of PDK1. These molecular changes in the ileum are simply one of a host of mechanisms working in concert with one another by which ciprofloxacin treatment mitigates body weight loss and drastically enhances subsequent survival after combined injury. To this end, our findings indicate that oral treatment of ciprofloxacin is a valuable therapeutic treatment after irradiation with combined injury and warrants further analyses to elucidate the precise mechanisms involved.

Radiation mitigating properties of the lignan component in flaxseed.

BACKGROUND: Wholegrain flaxseed (FS), and its lignan component (FLC) consisting mainly of secoisolariciresinol diglucoside (SDG), have potent lung radioprotective properties while not abrogating the efficacy of radiotherapy. However, while the whole grain was recently shown to also have potent mitigating properties in a thoracic radiation pneumonopathy model, the bioactive component in the grain responsible for the mitigation of lung damage was never identified. Lungs may be exposed to radiation therapeutically for thoracic malignancies or incidentally following detonation of a radiological dispersion device. This could potentially lead to pulmonary inflammation, oxidative tissue injury, and fibrosis. This study aimed to evaluate the radiation mitigating effects of FLC in a mouse model of radiation pneumonopathy. METHODS: We evaluated FLC-supplemented diets containing SDG lignan levels comparable to those in 10% and 20% whole grain diets. 10% or 20% FLC diets as compared to an isocaloric control diet (0% FLC) were given to mice (C57/BL6) (n=15-30 mice/group) at 24, 48, or 72-hours after single-dose (13.5 Gy) thoracic x-ray treatment (XRT). Mice were evaluated 4 months post-XRT for blood oxygenation, lung inflammation, fibrosis, cytokine and oxidative damage levels, and survival. RESULTS: FLC significantly mitigated radiation-related animal death. Specifically, mice fed 0% FLC demonstrated 36.7% survival 4 months post-XRT compared to 60-73.3% survival in mice fed 10%-20% FLC initiated 24-72 hours post-XRT. FLC also mitigated radiation-induced lung fibrosis whereby 10% FLC initiated 24-hours post-XRT significantly decreased fibrosis as compared to mice fed control diet while the corresponding TGF-beta1 levels detected immunohistochemically were also decreased. Additionally, 10-20% FLC initiated at any time point post radiation exposure, mitigated radiation-induced lung injury evidenced by decreased bronchoalveolar lavage (BAL) protein and inflammatory cytokine/chemokine release at 16 weeks post-XRT. Importantly, neutrophilic and overall inflammatory cell infiltrate in airways and levels of nitrotyrosine and malondialdehyde (protein and lipid oxidation, respectively) were also mitigated by the lignan diet. CONCLUSIONS: Dietary FLC given early post-XRT mitigated radiation effects by decreasing inflammation, lung injury and eventual fibrosis while improving survival. FLC may be a useful agent, mitigating adverse effects of radiation in individuals exposed to incidental radiation, inhaled radioisotopes or even after the initiation of radiation therapy to treat malignancy.

[Modern approaches to correction and prophylaxis of premature aging using adaptogenes of plant origin].

Last years, the big attention is given studying of the methods promoting increase of the immune status of an organism, got under influence of extreme factors, in particular, ionas radiations. In this connection perspectivity of application of laboratory diagnostics for testing a degree of defeat of immune system and application phytoadaptogenes is proved, namely: tinctures of a Panacis ginseng, Schizandrae chinensis, an extract Elaetherococcus for correction of such conditions.

[Radiation-protective action of bioantioxidant complex of ginseng extract in the model of the radiation-induced aging during development of radiation-induced neoplasms].

The study of the geriatric properties of the bioantioxidant complex "Neovitin" received from a biomass of ginseng, against formation of radio gene tumors was continued. The preparation was applied to the laboratory animals exposed to chronic gamma irradiation by low doses, by all period of irradiation and thirty days in the post beam period. The expressed anticancerogenic effect of "Neovitin", reducing formation of radio gene tumors, including malignant, as well as reduction of a spectrum of new growths were proved.

The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment.

PURPOSE: We hypothesized that administration of the angiotensin type 1 (AT1) receptor antagonist, L-158,809, to young adult male rats would prevent or ameliorate fractionated whole-brain irradiation (WBI)-induced cognitive impairment. MATERIALS AND METHODS: Groups of 80 young adult male Fischer 344 x Brown Norway (F344xBN) rats, 12-14 weeks old, received either: (1) fractionated WBI; 40 Gy of gamma rays in 4 weeks, 2 fractions/week, (2) sham-irradiation; (3) WBI plus L-158,809 (20 mg/L drinking water) starting 3 days prior, during, and for 14, 28, or 54 weeks postirradiation; and (4) sham-irradiation plus L-158,809 for 14, 28, or 54 weeks postirradiation. An additional group of rats (n = 20) received L-158,809 before, during, and for 5 weeks postirradiation, after which they received normal drinking water up to 28 weeks postirradiation. RESULTS: Administration of L-158,809 before, during, and for 28 or 54 weeks after fractionated WBI prevented or ameliorated the radiation-induced cognitive impairment observed 26 and 52 weeks postirradiation. Moreover, giving L-158,809 before, during, and for only 5 weeks postirradiation ameliorated the significant cognitive impairment observed 26 weeks postirradiation. These radiation-induced cognitive impairments occurred without any changes in brain metabolites or gross histologic changes assessed at 28 and 54 weeks postirradiation, respectively. CONCLUSIONS: Administering L-158,809 before, during, and after fractionated WBI can prevent or ameliorate the chronic, progressive, cognitive impairment observed in rats at 26 and 52 weeks postirradiation. These findings offer the promise of improving the quality of life for brain tumor patients.

Clindamycin and quinolone therapy for Bacillus anthracis Sterne infection in 60Co-gamma-photon-irradiated and sham-irradiated mice.

OBJECTIVES: Sublethal ionizing doses of radiation increase the susceptibility of mice to Bacillus anthracis Sterne infection. In this study, we investigated the efficacy of clindamycin in 60Co-gamma-photon-irradiated and sham-irradiated mice after intratracheal challenge with B. anthracis Sterne spores. Clindamycin has in vitro activity against B. anthracis and inhibits the production of toxin from other species, although no direct evidence exists that production of B. anthracis toxin is inhibited. METHODS: Ten-week-old B6D2F1/J female mice were either sham-irradiated or given a sublethal 7 Gy dose of 60Co-gamma-photon radiation 4 days prior to an intratracheal challenge with toxigenic B. anthracis Sterne spores. Mice were treated twice daily with 200 mg/kg clindamycin (subcutaneous or oral), 100 mg/kg moxifloxacin (oral), 50 mg/kg ciprofloxacin (subcutaneous) or a combination therapy (clindamycin + ciprofloxacin). Bacteria were isolated and identified from lung, liver and heart blood at five timed intervals after irradiation. Survival was recorded twice daily following intratracheal challenge. RESULTS: The use of clindamycin increased survival in gamma-irradiated and sham-irradiated animals challenged with B. anthracis Sterne in comparison with control mice (P < 0.001). Ciprofloxacin-treated animals had higher survival compared with clindamycin-treated animals in two experiments, and less survival in a third experiment, although differences were not statistically significant. Moxifloxacin was just as effective as clindamycin. Combination therapy did not improve survival of sham-irradiated animals and significantly decreased survival among gamma-irradiated animals (P = 0.01) in comparison with clindamycin-treated animals. B. anthracis Sterne was isolated from lung, liver and heart blood, irrespective of the antimicrobial treatment. CONCLUSIONS: Treatment with clindamycin, ciprofloxacin or moxifloxacin increased survival in sham-irradiated and gamma-irradiated animals challenged intratracheally with B. anthracis Sterne spores. However, the combination of clindamycin and ciprofloxacin increased mortality associated with B. anthracis Sterne infection, particularly in gamma-irradiated animals.

Erythropoietin restores the anemia-induced reduction in radiosensitivity of experimental human tumors in nude mice.

PURPOSE: The effect of recombinant human erythropoietin (rhEPO) on the radiosensitivity of human tumor xenografts growing in anemic and nonanemic nude mice was studied. METHODS AND MATERIALS: Anemia was induced by total body irradiation ([TBI], 2 x 4 Gy) of mice before tumor implantation into the subcutis of the hind leg. The development of anemia was prevented by rhEPO (750 U/kg s.c.) given 3 times weekly starting 2 weeks before TBI. Fourteen days after fractionated TBI (tumor volume of approx. 40 mm(3)), single-dose irradiation of the tumor with varying doses was performed so that in full dose-response relationship for the probability of tumor cure was obtained. RESULTS: Radiation-induced anemia (hemoglobin concentration [cHb] = 9.9 g/dl) led to a reduced radiosensitivity compared to controls [49.4 vs. 40.1 Gy radiation dose to control 50% of the tumors (TCD50)]. Upon rhEPO treatment for anemia prevention (cHb = 13.3 g/dl), the TCD50 was 39.8 Gy, illustrating restored radiosensitivity compared to anemic mice. CONCLUSION: These data provide further experimental evidence for restored radiosensitivity upon prevention of anemia with rhEPO.

Effects of oral arginine and glutamine on radiation-induced injury in the rat.

BACKGROUND: Exposure of the abdominal region to ionizing radiation is associated with serious untoward symptoms of intestinal dysfunction and some reports indicate that nutrient supplements may reduce these adverse effects. This study was designed to investigate the possible beneficial effects of oral arginine or glutamine supplementation on the radiation-induced tissue injury. MATERIALS AND METHODS: Rats were given one of three feeding regimens: standard diet and water (control group), diet and water containing 2% arginine (arginine group), diet and water containing 2% glutamine (glutamine group) for 3 days prior to radiation. All rats were then subjected to a single does of 1100 cGy to the abdomen. Several serum biochemical parameters and the histologic alterations in different segments of gastrointestinal tract and liver were measured 4 days after irradiation. RESULTS: All the arginine-fed rats developed diarrhea on Day 4 postirradiation, compared to 71% incidence in control rats and 86% in glutamine-fed rats. Serum levels of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the arginine group were markedly higher than those in other groups. On histological examination, radiation caused more serious damage to various segments of intestine in the arginine-fed rats compared to rats on other feeding regimens. CONCLUSION: These observations seriously question the beneficial effects of arginine and glutamine supplementations on radiation-induced tissue injury.

[Metabolic effect of amaranth oil and impulse hypoxic training under chronic fluoride intoxication and small doses of ionizing radiation]. / Metabolichni efekty oliï amarantu ta impul'snoho hipoksychnoho trenuvannia za umov diï ftorystoï intoksykatsiï ta malykh doz radiatsiï.

Lipid peroxidation and antioxidative defence system in blood, liver and heart tissues, nitric oxide metabolites content in brain tissue of rats under binary action of small-doses of ionizing radiation and fluoride intoxication treated by amaranth oil and interval hypoxic training have been studied. Complex using of amaranth oil and interval hypoxic training result in increase both enzymatic, as nonezymatic links of antioxidant defence in all investigated tissues. It was revealed also enhance of NO system metabolites content in brain gomogenate. In this conditions lipid peroxidation processes in liver and heart tissues normalize comparison with essential increase level LPO under binary action influence. On the basis of obtained results LPO metabolites content we can suppossed that complex using of amaranth oil and interval hypoxic training result in increase of organism adaptative possibility. This complex can be using for binary action of ionizing radiation and fluoride intoxication correction.

Single administration of thrombopoietin to lethally irradiated mice prevents infectious and thrombotic events leading to mortality.

A sufficiently high dose of thrombopoietin to overcome initial c-mpl-mediated clearance stimulates hematopoietic reconstitution following myelosuppressive treatment. We studied the efficacy of thrombopoietin on survival after supralethal total body irradiation (9 Gy) of C57BL6/J mice and the occurrence of infectious and thrombotic complications in comparison with a bone marrow graft or prophylactic antibiotic treatment. Administration of 0.3 microg thrombopoietin, 2 hours after irradiation, protected 62% of the mice as opposed to no survival in placebo controls. A graft with a supraoptimal number of syngeneic bone marrow cells (10(6) cells) fully prevented mortality, whereas antibiotic treatment was ineffective. Blood cell recovery was observed in the thrombopoietin-treated mice but not in the placebo or antibiotic-treated group. Bone marrow and spleen cellularity as well as colony-forming unit granulocyte-macrophage and burst-forming unit erythroid were considerably increased in thrombopoietin-treated mice relative to controls. Histologic examination at day 11 revealed numerous petechiae and vascular obstructions within the brain microvasculature of placebo-treated mice, which was correlated with hypercoagulation and hypofibrinolysis. Thrombopoietin treatment prevented coagulation/fibrinolysis disorder and vascular thrombosis. High fibrinogen levels were related to bacterial infections in 67% of placebo-treated mice and predicted mortality, whereas the majority of the thrombopoietin-treated mice did not show high fibrinogen levels and endotoxin was not detectable in plasma. We conclude that thrombopoietin administration prevents mortality in mice subjected to 9-Gy total body irradiation both by interfering in the cascade leading to thrombotic complications and by amelioration of neutrophil and platelet recovery and thus protects against infections and hemorrhages.

[An experimental study of the role of prostaglandins in the mechanism of the occurrence of dyspeptic disorders during the primary reaction after body exposure to ionizing radiation at large doses]. / Eksperimental'noe izuchenie roli prostaglandinov v mekhanizme vozniknoveniia dispepticheskikh narushenii v period pervichnoi reaktsii posle vozdeistviia na organizm ioniziruiushchikh izluchenii v bol'shikh dozakh.

The experiments with dogs exposed to 100 Gy of accelerated electrons demonstrated a significant role of prostaglandins in the origin of early post-radiation dyspepsia. Their significance for genesis of post-radiation dyspeptic disturbance caused by exposure to superhigh doses becomes clear-cut when a combination of an antiemetic and inhibitors of prostaglandin biosynthesis is used. A study of the effect of dexamethasone, a blocker of arachidonic acid release, and of voltaren, an inhibitor of prostaglandin formation from cyclic endoperoxide, suggests that it would be appropriate to prevent radiation vomiting and diarrhea by inhibiting both of the above stages in prostaglandin biosynthesis.

[An experimental study of the role of a blockade of serotonin 5-HT3 receptors and dopamine D2 receptors in the mechanism of the occurrence of early radiation vomiting in monkeys]. / Eksperimental'noe izuchenie roli blokady 5-HT3-retseptorov serotonina i D2-retseptorov dofamina v mekhanizme vozniknoveniia rannei radiatsionnoi rvoty u obez'ian.

The experiments with M. fasciculata monkeys exposed to 137Cs gamma-radiation with a dose of 6.9 Gy showed that Latranum, a blocker of serotonin 5-HT3 receptors, is a more efficient antiemetic than Dimetphramidum, a D2 dophamin lytic. This is suggested by fewer animals with emetic reaction of by less severe vomiting in case they have any. The results agree well with a hypothesis that serotonin receptors are dominant in the chemoreceptor trigger zone of monkeys.

Protective and therapeutic effect of silymarin on the development of latent liver damage.

Radioprotective and therapeutical effect of silymarin (Flavobion) on development and repair of latent injury in rat liver was examined by its application during the continual gamma irradiation (dose rates 0.2 and 0.6 Gy/day) or after acute gamma irradiation (dose 6 Gy). Silymarin influence was evaluated on the basis of mitotic index and chromosomal aberration frequency in the liver regenerating after partial hepatectomy. We have found that silymarin application stimulates the process of liver regeneration in non-irradiated rats as well as in irradiated ones. Positive effect of silymarin (100 mg per kg p.o. ones per day) was manifested at both dose rates of continual irradiation with increase in mitotic activity and mitigation of chromosomal erration frequency in the regenerating liver in comparison with non-protected irradiated animals. Curative effect of silymarin (70 mg/kg p.o., twice per day) was shown especially after 14 days of its postradiation application.

[The mechanism of the occurrence of vomiting during the primary reaction after exposure of the body to ionizing radiations at large doses]. / O mekhanizme vozniknoveniia rvoty v periode pervichnoi reaktsii posle vozdeistviia na organizm ioniziruiushchakh izluchenii v bol'shakh dozakh.

In the experiments of dogs exposed to ionizing radiations at doses of 50 and 70 Gy, an essential role of the central mechanism in the origin of early postradiation vomiting has been confirmed. Insufficient efficiency of dimethpramide, a dophamynolytics, in this case may be connected either with initiation of other (non-dophamynosensitive) structures of the chemoreceptor trigger zone of with a growing role of the reflex way of vomiting arising due to a considerable intestinal injury that causes diarrhea. The inhibition of intestinal M-cholinoreceptors by methacine prevented diarrhea but didn't change the intensity of the vomiting reaction which, however, does not eliminate the possibility of afferentation from receptors that respond to others biologically active substances.

[An experimental study of the effect of Zofran on the manifestations of a primary reaction to irradiation]. / Eksperimental'noe issledovanie vliianiia zofrana na proiavleniia pervichnoi reaktsii na obluchenie.

Zofran is a selective antagonist of 5-HT3 receptors which effectively prevents postradiation dyspeptic and behavioral disorders in dogs and rats. Administration of the drug normalizes intestinal absorption and propulsion activity in irradiated animals.