NMR spectroscopy based metabolic profiling of urine and serum for investigation of physiological perturbations during radiation sickness

Radiation accidents are rare events that induce radiation syndrome, a complex pathology which is difficult to treat. In medical management of radiation victims, life threatening damage to different physiological systems should be taken into consideration. The present study was proposed to identify metabolic and physiological perturbations in biofluids of mice during different phases of radiation sickness using ¹H nuclear magnetic resonance (¹H NMR) spectroscopy and pattern recognition (PR) technique. The ¹H NMR spectra of the biofluids collected from mice irradiated with 5 Gray (Gy) at different time points during radiation sickness were analysed visually and by principal components analysis. Urine and serum spectral profile clearly showed altered metabolic profiles during different phases of radiation sickness. Increased concentration of urine metabolites viz. citrate, α ketoglutarate, succinate, hippurate, and trimethylamine during prodromal and clinical manifestation phase of radiation sickness shows altered gut microflora and energy metabolism. On the other hand, serum nuclear magnetic resonance (NMR) spectra reflected changes associated with lipid, energy and membrane metabolism during radiation sickness. The metabonomic time trajectory based on PR analysis of ¹H NMR spectra of urine illustrates clear separation of irradiated mice group at different time points from pre dose. The difference in NMR spectral profiles depicts the pathophysiological changes and metabolic disturbances observed during different phases of radiation sickness, that in turn, demonstrate involvement of multiple organ dysfunction. This could further be useful in development of multiparametric approach for better evaluation of radiation damage as well as for medical management during radiation sickness.     

Combined effect of normobaric hyperoxia and vibration on the radiosensitivity of animals

In experiments with hybrid mice (CBA X C57B1)F1 and F2(CBWA), a study was made of the combined effect of normobaric hyperoxia and vibration on sensitivity of the organism to gamma-radiation. A single and protracted (for 5 days, daily) vibration before irradiation aggravated acute radiation sickness. A modifying effect of hyperoxia on the development of the intestinal form of radiation sickness was the same as that observed under the effect of vibration. In the experiments with tetrahybrids, the combined effect of the two factors aggravated drastically the intestinal syndrome of acute radiation sickness (DMF = 1.24).     

Chronic radiation damage by uranium and plutonium nuclear fission products

Chronical radiation sickness is a special form of the radiation damage. It occurs when doses of chronical irradiation exceed their values established for professionals. The sickness is well studied in clinical observations. It may take place also if uranium and plutonium nuclear fission products (NFP) enter the organism. In the last case the chronical radiation sickness practically is not investigated. In the article we present the results of the experimental studies on dogs of the damage caused by NFP.     

Biochemical reception and ionizing irradiation of the body

The authors present the idea of the importance of studying the mechanism of biochemical reception of biologically active compounds (BAC) particularly the reception of prostaglandins after the effect of ionizing radiation on eucaryotes as a factor playing a significant role in understanding the radiation sickness pathogenesis. The perspectives of studying BAC reception are prognosticated for searching new radiomodifying agents (radioprotectors and means for treating radiation sickness).     

Effect of ionizing radiation on the functional state of the vascular-thrombocytic component of the hemostasis system

The influence of ionizing radiation (gamma-rays 60Co) on aggregation activity of the vascular wall and functional (aggregation) platelet activity was studied in the course of the development of acute radiation sickness. The decrease in the aggregation properties of the vascular wall and high functional activity of platelets were inversely proportional, correlating with the periods of acute radiation sickness development and depending on the radiation dose. It is suggested that the changes detected may play a role in the pathogenesis of the development of the postirradiation thrombohemorrhagic syndrome.     

Analysis of the modifying effect of liver injury on the course and outcome of acute radiation sickness

In studying the aggravating effect of liver injury on the development of radiation sickness in irradiated rats it was found that the death rate increased within the range of minimal and median lethal doses and was not associated with the aggravation of both the haematologic and the hemorrhagic syndromes; it was not related to infectious complications as well. The data are presented on auto-intoxication as a factor aggravating the outcome of the combined radiation injury.     

Influence of ginger rhizome (Zingiber officinale Rosc) on survival, glutathione and lipid peroxidation in mice after whole-body exposure to gamma radiation

The radioprotective effect of the hydroalcoholic extract of ginger rhizome, Zingiber officinale (ZOE), was studied. Mice were given 10 mg/kg ZOE intraperitoneally once daily for five consecutive days before exposure to 6-12 Gy of gamma radiation and were monitored daily up to 30 days postirradiation for the development of symptoms of radiation sickness and mortality. Pretreatment of mice with ZOE reduced the severity of radiation sickness and the mortality at all doses. The ZOE treatment protected mice from GI syndrome as well as bone marrow syndrome. The dose reduction factor for ZOE was found to be 1.15. The optimum protective dose of 10 mg/kg ZOE was 1/50 of the LD50 (500 mg/kg). Irradiation of the animals resulted in a dose-dependent elevation in the lipid peroxidation and depletion of GSH on day 31 postirradiation; both effects were lessened by pretreatment with ZOE. ZOE also had a dose-dependent antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli and Candida albicans.     

Delayed effects of acute radiation injuries by radioactive carbon (14C-glycine)

A study was made of late biological effects of radioactive carbon (14C-glycine) applied in acute doses. The course of radiation sickness, at its acute stage, is similar to that of acute radiation sickness caused by external gamma-irradiation. The recovery is slow, and the disease becomes chronic exhibiting metabolism disturbances and early death of animals. Radioactive carbon has a pronounced blastomogenic action.     

The distribution of radiation-induced breaks in the chromosomes of irradiated subjects

Distribution of radiation-induced breakpoints in chromosomes and its bands in persons recovered from acute radiation sickness and personnel from Chernobyl NPP were investigated using G-banding staining. The frequency of damaged bands and breakpoints in groups exposed to radiation was significantly higher as compared with the control group. It was shown that in exposed to radiation persons damage depends on its length. Most frequently damaged bands in the observed groups were determined. The G-negative bands and telomeres of chromosomes were more sensitive to radiation.     

Proteinase inhibitors of the blood plasma in the early period of the development of acute radiation sickness in monkeys

A study was made of the postirradiation kinetics of blood antiproteinase activity in monkeys (Macaca nemestrina). Whole-body uniform gamma-irradiation (LD100/45) was shown to induce a significant decrease in the activity of alpha 2-macroglobulin during the first 24 h following irradiation: the decreased activity level was retained throughout the entire latent period of radiation sickness. At the height of radiation sickness (the 7th-10th day) up to the animals' death, a sharp increase was registered in the activity of alpha 1-inhibitor of blood plasma proteinases. The authors discuss a pathogenetic role of the diminution of the inhibitory potential of blood in the course of radiation sickness.     

The RBE of 0.85-MeV neutrons in the cerebral form of radiation sickness in guinea pigs

The RBE coefficient of neutrons (0.85 MeV) was 1.87 in comparison with that of electron radiation (8 MeV) as determined by the death rate of guinea pigs with the cerebral form of radiation sickness. LD50/1.5 amounted to 43.2 and 80.7 Gy. The dynamics of clinical symptoms at the height of the disease is discussed.     

Multivariate statistical analysis of tissue basophils in acute radiation sickness

By means of mark scale estimation method, discriminant and factor analyses, changes in integral indices on the state of mast cells in the rat mesentery have been investigated in dynamics of medullary, intestinal and cerebral forms of an acute radiation sickness. The integral indices are calculated basing on the morphometric parameters of the cells, that are obtained after the histological preparations are treated in a special automatic system for analysing images. At the medullary form of the acute radiation sickness, the greatest structural rearrangements of the mast cells take place during the first hours after the radiation, as well as during the climax of the disease, at the intestinal form, the analogous changes are revealed 1-3 days after the effect, and at the cerebral form--3 h after the radiation. The integral indices, calculated by means of the three methods, are well correlated with each other.     

A possibility to predict the severity of individual damage following the exposure to supralethal radiation dosage. Prediction of working capacity of irradiated rats and dogs by response to pre-exposure hypobaric load

In experiments on rats and dogs exposed to radiation doses which cause intestinal and cerebral forms of radiation sickness, hypobaric hypoxia used as an unconventional test of animals' reactivity has enabled the relationship between reactivity and radiosensitivity to be established. Higher post-radiation efficiency is observed in animals with less pronounced changes during a barotest. The goodness of fit of experimental data to the expected result is up to 70%, rising if a set parameters for one index or the sum total of indices are used.     

15 years after the accident at the Chernobyl Nuclear Power Plant

Health effects as a result of the accident at the Chernobyl nuclear power plant occurred in 1986 are considered in the paper. Wrong prognosis of the health effects with respect to mortality and morbidity among the population exposed to low radiation doses is shown. Proven increase in thyroid cancer cases among people who were children aged from 0 to 18 at the time of the accident is shown. Linear relationship between thyroid cancer cases and dose to thyroid ranged from 0.2 to 4.0 Gy is considered. An additional absolute risk of thyroid cancer in children varies in the range 1.9-2.6 cases per 10(4) person-year Gy. During the fifteen years following the accident no cases of acute and chronic radiation sickness have been revealed because the population living in contaminated areas received low radiation doses. Also, exposures to low radiation doses did not result in excess of malignant tumors among population. In some cases the outcomes of acute radiation sickness were as follows: radiation damages to the skin, cancer cataracts, development of oncopathology.     

核辐射对大深度快速上浮脱险致减压病大鼠相关指标的影响*

目的: 探讨不同剂量核暴露后不同时间对大深度快速上浮脱险致减压病大鼠模型的发病率、死亡率及损伤指标的影响。方法: 80只SD雄性大鼠,随机分成空白对照组、脱险对照组和6个干预组(4 Gy辐射后4 h脱险、6 Gy辐射后4 h脱险、12 Gy辐射后4 h脱险、4 Gy辐射后8 h脱险、6 Gy辐射后8 h脱险、12 Gy辐射8 h后脱险),每组10只。干预组动物先采用不同剂量γ射线外照射(4、6、12 Gy),再进行大深度快速上浮脱险实验(最大加压深度150 m),分析大鼠肺W/D、脾指数及血浆IL-1β的变化。结果: 与脱险对照组比较,核辐射后脱险大鼠的减压病发病率及死亡率明显上升。4 Gy、6 Gy照射4 h后上浮脱险的大鼠发病率和死亡率较照射8 h后高。12 Gy辐射后4 h及8 h脱险大鼠的减压病的发病率及死亡率均比低剂量照射组明显增高,死亡率尤其明显。和发病率及死亡率的变化相一致,肺组织湿/干比、肺组织病理损伤程度、脾指数下降也表现同样的变化趋势:较低剂量(4 Gy、6 Gy)辐射后4 h改变明显,8 h改变不明显,而高剂量(12 Gy)辐射后4、8 h均变化明显。和空白对照组及脱险对照组相比较,各辐射后脱险组的血浆IL-1β浓度均显著上升。结论: 核辐射引起放射性肺损伤、免疫功能下降及血浆炎症因子浓度升高,会增加大鼠快速上浮脱险致减压病的风险。     

Changes in the dog endocrine system in the hematopoietic form of radiation sickness

The endocrine status of the organism estimated by the cortisol, insulin and triiodothyronine content of blood considerably changes during radiation sickness. The most pronounced changes in the endocrine status occur during the primary response and at the height of radiation sickness. The endocrine status test may be used in the individual radiosensitivity prognosis.     

Morphofunctional characteristics of the cells of the APUD system of the adrenal glands and the duodenum in the cerebral form of acute radiation sickness

Changes of a phase nature develop in the APVD system cells of rats, dogs, and monkeys exposed to electron radiation of doses inducing a cerebral form of radiation sickness. These changes in the morphofunctional status of APVD system cells may be considered as a syndrome displaying acute radiation apudopathies.     

A possible approach to large-scale laboratory testing for acute radiation sickness after a nuclear detonation

After the detonation of an improvised nuclear device, several key actions will be necessary to save the greatest number of lives possible. Among these tasks, the identification of patients with impending acute radiation sickness is a critical problem that so far has lacked a clear solution in national planning. We present one possible solution: the formation of a public-private partnership to augment the capacity to identify those at risk for acute radiation sickness.     

Sympathetic hyperfunction causes increased sensitivity of the autonomic nervous system to whole-body X irradiation

Although the etiology of radiation sickness is still unknown, disturbance of the autonomic nervous system is suggested to be a factor. This study was designed to compare the radiosensitivity of spontaneously hypertensive rats possessing sympathetic hyperfunction and control Wistar-Kyoto rats, and to analyze the effects of radiation on the autonomic nervous system in both strains. After a 7.5-Gy dose of whole-body X irradiation, the blood pressure decreased significantly at 8 h and 2 days in the spontaneously hypertensive rats, but not in the Wistar-Kyoto rats. Epinephrine levels in the adrenal gland of spontaneously hypertensive rats decreased at 4, 8 and 24 h, unlike the Wistar-Kyoto rats. Radiation evoked a stronger increase in norepinephrine in the jejunum and colon of spontaneously hypertensive rats than in Wistar-Kyoto rats. Acetylcholine levels in the jejunum of spontaneously hypertensive rats decreased, in contrast to the increase in Wistar-Kyoto rats within 24 h after irradiation. The survival rate of spontaneously hypertensive rats was lower than that of Wistar-Kyoto rats and weight loss, appetite loss and morphological changes in the jejunum were greater in spontaneously hypertensive rats than in Wistar-Kyoto rats after irradiation. These results indicated that X irradiation caused greater activities in autonomic nervous function and severe radiation injury in spontaneously hypertensive rats. Sympathetic hyperfunction may be associated with a higher sensitivity to radiation, including radiation injury and radiation sickness.