The effect of combined application of quercetin and indralin on postradiation repair of the hematopoietic system in acute radiation sickness

Hybrid F1 mice (CBA × C57Bl/6) were subjected to irradiation at a nonlethal dose of 6.7 Gy that brought on acute radiation sickness. In the experiments performed, we observed the beneficial effect of combined application of quercetin injected 30–60 min prior to irradiation with γ rays and the emergent radioprotector indralin injected after irradiation on development of postradiation repair in hematopoietic tissue. This effect was expressed as accelerated formation of endogenous spleen colonies and recovery of spleen weight and attenuation of leucopenia 12 and 16 days after acute irradiation. Treatment with only quercetin was not radioprotective.     

Radioprotective properties of indralin combined with cystamine and mexamine

The study of indralin radioprotective properties at its joint application with cystamine and mexamine was carried out in the experiments on inbred mice and rats. The mice and rats were exposed to whole-body y-irradiation at a dose of 9.0 and 9.5 Gy, correspondingly. A combined parenteral administration ofindralin and cystamine at a dose of 25 mg/kg showed ponentiaton of indralin radioprotective properties up to a level of the ED50 effect versus the absence of or a weak radioprotective effect in the case of their separate application. In the experiments on rats, indralin (50 mg/kg) and mexamine (12 mg/kg) injected intraperitoneally almost completely eliminated the animal mortality from the intestinal syndrome of acute radiation sickness amounting in the control radiation group to 60% on the 7th day after exposure to radiation at a dose of 9.5 Gy. However, at the above conditions, radioprotectors at these doses had a low-level radioprotective action at the onset of the bone marrow syndrome of acute radiation sickness. Combined application of indralin and mexamine at the same doses and at the same conditions led to a radiation protection 50% as high as in the case when radioprotectors were applied separately at a double dose.     

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.     

The influence of combined application of quercetin and indralin on post-irradiation repair of hematopoiesis in acute radiation injury

Experiments on mice-hybrids F1(CBA x C57B1/6) have detected a favorable effect of the associated application of quercetin (30-60 minutes before y-exposure of an animal) and a radioprotectant of urgent action indralin (in the case of its application after y-exposure) on a post-irradiation repair of the hematopoietic tissue in acute radiation sickness after y-exposure at a non-lethal dose of 6.7 Gy, which manifested itself in the accelerated formation of endogenous spleen colonies and spleen mass recovery, as well as in the lesser degree of leukopenia on the 12th and the 16th day after acute radiation injury. Quercetin per se did not have a radio-protective effect.     

Combined effect of interferon inducers, radiosensitizing and antineoplastic agents on solid tumors

In experiments with mice bearing solid sarcoma 37 a study was conducted on the combined effect of radiation and inductors of endogenous interferon synthesis (IEIS), together with hyperthermia or together with an alkylating and carbomoilating agent, dimethinur. The effect was estimated by the tumor growth coefficient and by the number of animals with the regressed tumors. Po I. polyC was not shown to influence the efficiency of hyperthermia combined with radiation; dextransulphate and tiloron increased the radiosensitizing effect of hyperthermia. Dimethinur aggravated the effect of radiation, but with IEIS used together with dimethynur and radiation, the response of the tumor increased insignificantly as compared to the effect of IEIS together with radiation.     

Antiradiation effects of leucynferon on dogs and guinea pigs

In experiments with two species of animals (dogs, guinea pigs) irradiated with sublethal and lethal doses of gamma-rays, it was observed, that leucynferon had antiradiation effect. Course of injections: dogs--8 injections subcutaneus: 2.0 ml (1, 3, 5, 8, 12, 14, 21, 34 days after irradiation); guinea pigs--14 injections subcutaneus, 0.2 ml (1-14 days after irradiation). Therapeutical effect was explained by capacity of the preparation to defend the hemopoietic organs from the radiation and to stimulate hemopoiesis. Leucynferon hindered the development of acute radiation sickness symptoms. Immunoreactivity of dogs and guinea pigs in experimental group was more complete and restored faster. The growth of the automicroflora on the skin was restrained. Production of interferon-gamma (which is a function of T-lymphocytes) was restored faster.     

Mechanisms of the protective action of sulfur-containing radioprotectors on the intestinal epithelium

In studying the influence of cystamine and gammaphos on the recovery of mouse jejunum epithelium after irradiation with doses inducing intestinal form of acute radiation sickness, it was shown that the radioprotective agents did not influence D0 value for intestinal epithelium stem cells, but in crypts the number of DNA-synthesizing enterocytes that entered mitosis increased after the preventive administration of the radioprotectors. All this caused the number of cells per villus to increase and intestinal mucosa to recover more readily.     

Selected contribution: Peripheral chemoreflex function in high-altitude natives and patients with chronic mountain sickness.

Peripheral chemoreflex function was studied in high-altitude (HA) natives at HA, in patients with chronic mountain sickness (CMS) at HA, and in sea-level (SL) natives at SL. Results were as follows. 1) Acute ventilatory responses to hypoxia (AHVR) in the HA and CMS groups were approximately one-third of those of the SL group. 2) In CMS patients, some indexes of AHVR were modestly, but significantly, lower than in healthy HA natives. 3) Prior oxygenation increased AHVR in all subject groups. 4) Neither low-dose dopamine nor somatostatin suppressed any component of ventilation that could not be suppressed by acute hyperoxia. 5) In all subject groups, the ventilatory response to hyperoxia was biphasic. Initially, ventilation fell but subsequently rose so that, by 20 min, ventilation was higher in hyperoxia than hypoxia for both HA and CMS subjects. 6) Peripheral chemoreflex stimulation of ventilation was modestly greater in HA and CMS subjects at an end-tidal Po(2) = 52.5 Torr than in SL natives at an end-tidal Po(2) = 100 Torr. 7) For the HA and CMS subjects combined, there was a strong correlation between end-tidal Pco(2) and hematocrit, which persisted after controlling for AHVR.     

"Ischemia/reperfusion" for stem cells of two "critical" cell renewal systems of organism

In this article is presented the result of the experiments on mice-hybrids F1(CBA x C57B1/6), which indicates the presence of the reaction of "ischemia/reperfusion" for stem cells of two "critical" cell renewal systems of organism (bone marrow and intestinal epithelium) during the irradiation under the conditions of hypoxic radioprotector application. The additional injection of the source of nitric oxide radicals-sodum nitroprusside (SNT) to the mice right after the irradiation under the conditions of hypoxic protection by serotonin, resulted the substantial increase of the survival rate of hematopoietic stem cells (registered by the methods of endogenous and exogenous colony forming in spleen) and stem cells of intestinal epithelium (registered by the method of intestinal "microcolonies"). The similar radioprotective effect was also registered during the test of survival rate of mice under tests of "bone marrow" and "intestinal" forms of radiation lethality that is evidence of the importance of the realization of phenomenon "ischemia/reperfusion" in the reaction of whole organism on the acute radiation injury. As SNP weakens the manifestation apoptosis and necrosis through competition with active forms of oxygen (AFO) during the period of "reperfusion" on basis of the found out phenomenon experimental model for studying mechanisms of stem cells damage in vivo induced by AFO and for the search of the modifiers weakening or strengthening such damage can be developed.     

Changes in labrocytes during acute radiation sickness (morphometric study)

Changes in the morphometric parameters of rat mast cells during acute radiation sickness have been studied. The most significant deviation of the quantitative indices of mast cells from the control values were noted at the height of the bone-marrow, at the terminal stage of the intestinal, and during the first few hours of the cerebral forms of acute radiation sickness.     

Differential effects of acute hypoxia and high altitude on cerebral blood flow velocity and dynamic cerebral autoregulation: alterations with hyperoxia.

We hypothesized that 1) acute severe hypoxia, but not hyperoxia, at sea level would impair dynamic cerebral autoregulation (CA); 2) impairment in CA at high altitude (HA) would be partly restored with hyperoxia; and 3) hyperoxia at HA and would have more influence on blood pressure (BP) and less influence on middle cerebral artery blood flow velocity (MCAv). In healthy volunteers, BP and MCAv were measured continuously during normoxia and in acute hypoxia (inspired O2 fraction = 0.12 and 0.10, respectively; n = 10) or hyperoxia (inspired O2 fraction, 1.0; n = 12). Dynamic CA was assessed using transfer-function gain, phase, and coherence between mean BP and MCAv. Arterial blood gases were also obtained. In matched volunteers, the same variables were measured during air breathing and hyperoxia at low altitude (LA; 1,400 m) and after 1-2 days after arrival at HA ( approximately 5,400 m, n = 10). In acute hypoxia and hyperoxia, BP was unchanged whereas it was decreased during hyperoxia at HA (-11 +/- 4%; P < 0.05 vs. LA). MCAv was unchanged during acute hypoxia and at HA; however, acute hyperoxia caused MCAv to fall to a greater extent than at HA (-12 +/- 3 vs. -5 +/- 4%, respectively; P < 0.05). Whereas CA was unchanged in hyperoxia, gain in the low-frequency range was reduced during acute hypoxia, indicating improvement in CA. In contrast, HA was associated with elevations in transfer-function gain in the very low- and low-frequency range, indicating CA impairment; hyperoxia lowered these elevations by approximately 50% (P < 0.05). Findings indicate that hyperoxia at HA can partially improve CA and lower BP, with little effect on MCAv.     

Quantitative regularities of development of endogenous infection in irradiated organism (survey of literature)

Statistical analysis of data from the literature and the author's own experimental results was carried out in order to reveal functional dependence between the dose of irradiation and the development of endogenous infection in an irradiated organism. Direct linear dependence was established between the dose of irradiation and the severity of endogenous infection at doses causing death from the "bone-marrow" syndrome in acute radiation sickness. In the case of death from the "intestinal" syndrome, inverse linear dependence can be observed between the dose of irradiation and the culture yield of microbes from internal organs. In this case, the pathological effect on the organism is due to bacterial endotoxins formed during disintegration of microbial cells in the organism. Endogenous infection and endotoxinaemia essentially aggravate the course of acute radiation disease. The importance of endogenous infection in death of the organism is neutralized after irradiation in doses causing death "under the ray".     

Mechanism of circulatory disorders in animals irradiated at high doses

Some data are reported on pathoanatomical changes, a status of the microcirculatory channel and the coagulogram of animals affected by high doses of ionizing radiation. The signs of disseminated intravascular blood coagulation have been revealed. The authors discuss the relationship between clinical manifestations with coagulopathy development and circulatory disturbances during intestinal and cerebral forms of acute radiation sickness.     

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.     

Effect of different doses of ionizing radiation on the binding of prostaglandin E2 in mouse tissues

The effect of various radiation doses on membrane reception of prostaglandin E2(PGE2) of spleen, small intestine, brain, and liver cells of mice was studied in dynamics. Irradiation of the animals with doses producing bone marrow, intestinal and cerebral forms of radiation sickness was shown to change specific binding of PGE2 to cell membranes of both radiosensitive tissues and a relatively radioresistant organ, the liver.     

Differential regulation of prostacyclin and thromboxane by dexamethasone and celecoxib during oxidative stress in newborn rabbits

To compare the effects of dexamethasone (Dex) and celecoxib (Cel) on F-isoprostane, prostacyclin (PGI2), and thromboxane A2 (TxA2) following hyperoxia, and hyperoxia followed by recovery in room air (RA), newborn rabbits were exposed to hyperoxia (80-100% oxygen) for 4 days, during which they were treated with saline (Sal, i.m.), Dex (i.m.), vehicle (Veh, PO), or Cel (PO, n = 12 per group). Six animals in each group were sacrificed immediately following hyperoxia, and the remainder allowed to recover in RA for 5 days. The control litters were treated simultaneously in RA with all conditions other than atmospheric oxygen being identical. Blood samples were assayed for 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), 6-keto prostaglandin F1alpha (6-ketoPGF1alpha), and TxB2. Dex and Cel decreased 8-epi-PGF2alpha during hyperoxia and the recovery period. Dex increased 6-ketoPGF2alpha following hyperoxia, while similar increments were noted during recovery with Cel. Although TxB2 was decreased only during the recovery period, TxB2/6-ketoPGF1alpha ratio was lower during hyperoxia and recovery in both treated groups. The effect of Cel on 8-epi-PGF2. and TxA2/PGI2 ratio confirm the formation of a COX-derived F2-isoprostane that is possibly linked to TxA2 receptors. Further studies are required to examine whether Cel can be used as a therapeutic alternative to Dex for oxygen-induced injury in the newborn.     

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.     

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.     

Efficiency of polysaccharide translam for early treatment of acute radiation illness

Antiradiation therapeutic efficiency of translam (1-->3; 1-->6-beta-D-glucan) produced by enzymatic synthesis out of laminarin, polysaccharide of Laminaria cychorioides, has been studied in four animal species (mice, guinea-pigs, dogs, monkeys). A stable curative effect has been observed following its administration within first 24 h after radiation exposure at doses that cause acute radiation sickness (about LD90). The preparation is nontoxic and has a broad therapeutic range which permits its practical application.