Mitigating Effect of Nitrates (Monizol) on Pharmacodynamic Shifts in the Cardiovascular System Caused by Radioprotector Indralin.

We studied the effect of radioprotector indralin (B-190) alone or in combination with monizol on BP and HR in rabbits, reduction of blood supply and spleen weight in rats and (CBA×C57Bl/6)F1 hybrids mice, and on blood loss from a wound on tip of the tail in mice. Being an α1-adrenomimetic, indralin caused hypertensive reaction with the development of bradycardia, reduced blood supply and spleen weight, and sharply reduced blood loss from the wound. Monizol as nitrate reduced BP without affecting HR and reduced blood loss from the wound. Monizol administered prior to indralin eliminated radioprotector-induced hypertensive reaction, reduced bradycardia by more than 2 times, and attenuated the effect of indralin on spleen weight and blood loss from the wound by 1.6-1.8 times. Monizol administered after indralin had no effect on shifts in peripheral blood supply caused by the radioprotector.

Therapeutic effect of long-term melatonin treatment on the course and fatal outcome of modeled acute radiation sickness.

We studied the effect of long-term administration of melatonin to male C57Bl/6 mice starting from day 3 after whole-body γ-irradiation (9.5-10.0 Gy, 7.7-17.1 cGy/min). It was found that replacement of drinking water with melatonin solution (5 mg/liter) did not reduce the amount of fluid intake throughout the period of acute radiation injury. The daily dose of melatonin was 0.9-1.2 mg/kg body weight (this parameter was lower at the peak of the disease and increased during the recovery stage). Melatonin by more than 20% (p<0.05) improved survival of mice exposed to γ-irradiation in a dose of LD97/30, reduced leukopenia during the stage of acute manifestations of the disease and maximum mortality, and increased blood leukocyte count by 40% (p<0.05) by day 12 after irradiation.

[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.

Effect of radioprotector Indralin on the course of acute GVH disease.

The effect of radioprotector indralin on the graft-versus-host reaction was studied on the model of acute GVH disease induced in mice by intraperitoneal transplantation of 40x10(6)semiallogenic splenocytes. The effect was evaluated by animal mortality from GVH disease. Recipients were male F1(CBAxC57Bl/6) mice exposed to 7 Gy 24 h before transplantation. Donors were male C57Bl/6 mice. Indralin, intraperitoneally injected in a dose of 100 mg/kg 5 min after irradiation attenuated the severity of GVH disease. It eliminated phase I of acute GVH reaction and shifted to the right the dynamics of mortality. Estimated time of 50% mortality (LT50) was prolonged by more than 4 days (the parameter increased by 31.1%). Two (5.7%) animals recovered from acute GVH disease, while all controls died. Indralin treatment after irradiation resulted in a 30% increase in survival of exposed mice.

[The characteristic of radioprotective properties of a radioprotectant B-190 at its administration after radiation].

In experiences on mice F1 (CBAxC57B 1/6) at a gamma-irradiation in a lethal dose LD(35-70/30) the radioprotectant B-190 at administration after an exposure would rise an animal survival--on 35-55%, caused the increase of the amount of endogenic colony in a spleen and of leucocytes in blood on 11th and 30th day of an acute radiation desease accordingly. The drug has the effect in the interval of doses from 75 up to 150 mg/kg b.w. with the rise of radioprotective action on dose reduction factor from 1.1 up to 1.22. alpha(1)-adrenoblockers terasosin in a dose of 15 mg/kg b.w. partially would reduce radioprotective properties of B-190 as radioprotectant or and drug of early therapy of acute radiation desease.

In vitro response of mitochondrial succinate oxidase system to epinephrine in human blood lymphocytes from health individuals and patients with neurocirculatory dystonia.

Activities of succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (hyaloplasmic and mitochondrial: alpha-GPDHH and alpha-GPDHM) in peripheral blood lymphocytes, and the response of SDH activity to exogenous epinephrine in vitro (the epinephrine test) were studied in 20 healthy subjects and 46 patients with hypertensive neurocirculatory dystonia. Activities of SDH, alpha-GPDHH, and alpha-GPDHM in blood lymphocytes and SDH adrenoreactivity in epinephrine test were higher in patients than in healthy controls. Treatment with hypotensive agents (isradipin and pyrroxan) moderated adrenoreactivity. Phytotherapy normalized the baseline activities of succinate oxidase system and alpha-glycerophosphate pathway in blood lymphocytes.

[The role of cell hypoxia in the effect of radiation protectors]. / Rol' kletochnoi gipoksii v protivoluchevom éffekte radioprotektorov.

In experiment with mice, rats and dogs the intimate relationship has been established between radioprotective efficiency of indraline, cystamine and mexamine and its properties to enhance succinate dehydrogenase (SDG) activity of blood lymphocytes (r = 0.95). In that analysis modifying effect of normobaric hyperoxia has been estimated. Mice and dogs were correspondingly irradiated with gamma-60Co-rays in the dose 8.33 and 3.16 Gy. In the investigation involving mice, dogs and men the effect-dose dependence of aggravating of the SDG activity was linear for indraline, but not for cystamine. In man hypoxic hypoxia with air-hypoxic mixture containing 10% of oxygen has initiated rise of the SDG activity being twice as smaller as the one when indraline in the dose of 100 mg administrated. Hyperoxia suppressed radioprotective properties of indraline, cystamine and mexamine in the ED50 in term of DRF by twice and didn't virtually influenced on that in the optimum radioprotective doses. Hyperoxia and alpha-adrenoblocator tropaphene also suppressed the SDG response to indraline. In vitro experiment cystamine and adrenaline held stimulating action on SDG of blood lymphocytes. The role of pharmacological stimulation of cell respiration and cell hypoxia relating with the one in mechanism of radioprotective effect of the radioprotector of two dissimilar groups was discussed.

[Studies of the radiation-protective effects of indralin on the hematopoietic system of different species of animals]. / Issledovanie radiozashchitnogo éffekta indralina na krovetvornoi sisteme u razlichnykh vidov zhivotnykh.

The experiments were made on mice, guinea pigs and dogs. Radioprotector indraline increased radioresistant state of hematopoietic stem cells in vivo and in vitro, decreased the amount of post-radiation chromosome aberrations in marrow, induced more early and intensive post-radiation proliferative repair of marrow and spleen, faster regeneration of the initial amount of leukocytes, thrombocytes and erythrocytes in blood of mice, guinea pigs and dogs. Antiradiation efficiency of indraline in hematopoietic system is equal to 1.5-2 by FMD. Radioprotective mechanism of indraline effect on hematopoietic system is discussed.

[Some mechanisms of pathogenesis of hypertonic type neurocirculatory dystonia in flying personnel]. / Nekotorye mekhanismy patogenesa neirotsirkuliatornoi distonii gipertonicheskogo tipa u letnogo sostava.

Cytochemical analysis was used to compare the activities of hyaloplasmatic and mitochondrial glycerophosphate dehydrogenase, and succinate dehydrogenase in lymphocytes of peripheral blood taken from 14 aviators with the diagnose of hypertonic neurocirculatory dystonia, and 18 healthy aviators. Significantly higher activity of these enzymes in patients is assumed to signify intensification of metabolism and cellular respiration bearing the forced adaptive character. On this evidence, an attempt is made to interpret earlier discovered changes in the immunobiochemical status of these patients and plausible mechanisms of progressive arterial hypertension are hypothesized. Emphasis is laid on the necessity to direct secondary preventive measures at the early phases of hypertension not only on reduction of the vascular tone and correction of the immunobiochemical status but on building-up of cell's functional reserves.

[Biochemical evaluation of various respiration conditions during simulation of extended flight]. / Biokhimicheskaia otsenka razlichnykh rezhimov dykhaniia v usloviiakh modelirovaniia dlitel'nogo poleta.

During a simulated long-term mission with participation of male volunteers biochemical effects of various conditions of oxygen supply including breathing the cabin air at 2.4 km, pure oxygen, and intermittent hypoxia/hyperoxia, i.e. breathing the cabin air for 50 min and pure O2 for 10 min every hour in flight were studied. This assessment of respiration conditions by biochemical criteria allowed to recognize the combination of short hyperoxia and cabin air as the optimum to be taken into accounted in attacking the problem of oxygen supply of aviators in extended flights.

[Mechanism of the radiation-protective effect of indralin]. / K mekhanizmu protivoluchevogo deistviia indralina.

Pharmacological test demonstrated that radioprotective activity of indralin occurs by interaction with alpha-adrenoreceptor. Radioprotective effect of indralin decreased by alpha-adrenoblocker, aminazine and theophylline. Normobaric hyperoxia during irradiation reduced radioprotective effect of indralin in doses about ED50. In experiment with mice and rats it was shown that indralin induced acute hypoxia, impaired oxygen consumption and heat production by 30-46%, spleen bloodflow to 26.3% of control level, rectal temperature by 1.5-2 degrees C (mouse). After 30-min indralin raised resistance of mice to hypoxic hypoxia that is believed due to rapid development of biochemical adaptive process in hypoxic cells.

[The effect of emotional stress on the hormonal status indices, the level of cyclic nucleotides and the content of beta 2-microglobulin in the blood and thymic tissue during the use of a synthetic analog of thyroliberin]. / Vliianie émotsional'nogo stressa na nekotorye pokazateli gormonal'nogo statusa, uroven' tsiklicheskikh nukleotidov i soderzhanie beta 2-mikroglobulina v krovi i tkani timusa pri primenenii sinteticheskogo analoga tiroliberina.

After experiencing a conflict situation once or daily for 5 days, rats were divided into a group resistant to stress and a group predisposed to stress according to the post-stress involution of the thymus. Changes in biochemical values were revealed in emotional stress. Significant drop in the blood insulin level, a high cAMP/cGMP ratio level, and reduction of the beta 2-microglobulin level and the level of circulating immune complexes were found. The preparation PR-546 caused an increase of the insulin level in intact and experimental rats, which, however, did not lead to diminution of the stress reaction.

[Effect of adrenaline on the succinate dehydrogenase activity of peripheral blood lymphocytes of rats following exposure to ionizing radiation]. / Vliianie adrenalina na aktivnost' suktsinatdegidrogenazy v limfotsitakh perifericheskoi krovi krys posle vozdeistviia ioniziruiushchego izlucheniia.

In experiments with albino mongrel female rats, the influence of adrenaline on succinate dehydrogenase (SDG) activity in the peripheral blood lymphocytes of irradiated and intact animals has been investigated. Two minutes after the intraperitoneal administration of adrenaline (1 mg/kg) to intact rats SDG activity sharply rises and 3-4 min it drastically falls. In 6 to 8 min the second peak in the enzyme activity is registered. Twenty minutes after irradiation of rats in the cranio-caudal direction with a dose of 75 Gy delivered to head, the reaction to adrenaline, manifested by the rise in SDG activity, is absent.

[Change in the succinate dehydrogenase activity of peripheral lymphocytes in the rat in early periods following exposure to ionizing radiation]. / Izmenenie aktivnosti suktsinat-degidrogenazy v limfotsitakh perifericheskoi krovi krys v rannie sroki posle vozdeistviia ioniziruiushchego izlucheniia.

Activity of succinate dehydrogenase (SDH) in peripheral blood lymphocytes of albino mongrel rats was determined during an hour following gamma-irradiation. The highest SDH activity in blood lymphocytes (a 41 per cent increase) was registered 20-30 min following 75 Gy irradiation of the head. With a dose of 20 Gy the SDH response was twice as low. During 1 h following irradiation with a dose of 200 Gy the SDH activity exhibited a 10 per cent decrease.

[Radiosensitivity of animals irradiated in different gaseous media. Effect of repeated short-term breathing of pure oxygen on radiosensitivity]. / Radiochuvstvitel'nost' organizma pri obluchenii zhivotnykh v izmenennoi gazovoi srede. Vliianie povtornogo kratkovremennogo dykhaniia chistym kislorodom na radiochuvstvitel'nost' zhivotnykh.

Radioresistance of (C57Bl/6 X A/SnY)F1 and (BALB/c X BioCW/Y X CC57W X A/SnY)F2 female mice decreased after repeated (in 48 hr for 2 weeks) short-term (10-20 min) normal pressure oxygen breathing. Repeated 10-min exposures to pure oxygen had a negative effect on the course of the bone-marrow and intestinal forms of acute radiation sickness.

[Biological effects of the action of a high-tension DC electrical field]. / Nekotorye biologicheskie éffekty deistviia postoiannogo élektricheskogo polia vysokoi napriazhennosti.

The experiments were carried out on 345 white mice using hematological and pathomorphological procedures. The constant electric field (CEF) was generated in a special laboratory device. The exposure to CEF of 50 and 100 kV/m for 20 s caused hematological and morphological changes typical of the anxiety stage of the adaptation syndrome. The exposure also produced morphological changes of reactive and destructive type in skeletal muscles and different segments of kinesthetic receptors. The level of the above changes appears to be directly related to the CEF strength.