Effect of α1-Adrenomimetic Indralin on Oxygen Consumption by Bone Marrow Cells in Vitro

Ушаков, И. Б.; Korovkina, E. P.; Kovtun, V. Iu.

doi:10.1007/s10517-013-2153-x

Cited by 6 publications

(4 citation statements)

References 2 publications

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“…Adrenaline activates oxidative phosphorylation through α 1 -adrenoceptors [ 106 ]. Indralin increases oxygen consumption in bone marrow cells in vitro by up to 50% when tissue oxygen tension is lower than 10 µmol [ 107 ]. Myeloid multipotent progenitors and pluripotent stem cells [ 108 ] have α 1 -adrenergic receptors that realize a similar scenario.…”

Section: Reviewmentioning

confidence: 99%

Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals

Ушаков

2014

Journal of Radiation Research

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This review gives a comparative evaluation of the radioprotective properties and the therapeutic index (TI) of radioprotectors from various pharmacological group in experiments on both small and large animals. It presents a hypothesis explaining the decrease in the TI of cystamine and 5-methoxytryptamine (mexamine), and the retention of that of α1-adrenomimetic indralin, and also compares the effects on large and small animals. The considerable differences in the therapeutic indices of catecholamines, serotonin and cystamine are a consequence of specific features of their mechanisms of radioprotective action. Radioprotectors acting via receptor mediation tend to provide a more expanded window of protection. The reduction in the TI of cystamine in larger animals, such as dogs, may be caused by the greater increase in toxicity of aminothiols in relation to the decrease in their optimal doses for radioprotective effect in going from mice to dogs, which is a consequence of the slower metabolic processes in larger animals. The somatogenic phase of intoxication by cystamine is significantly longer than the duration of its radioprotective effect, and increases with irradiation. The decrease in the radioprotective effect and the TI of mexamine in experiments with dogs may be caused by their lower sensitivity to the acute hypoxia induced by the mexamine. This is because of lower gradient in oxygen tension between tissue cells and blood capillaries under acute hypoxia that is determined by lower initial oxygen consumption in a large animal as compared with a small animal. Indralin likely provides optimal radioprotective effects and a higher TI for large animals via the increased specificity of its adrenergic effect on tissue respiration, which supports the development of acute hypoxia in the radiosensitive tissues of large animals. The stimulatory effect of indralin on early post-irradiation haematopoietic recovery cannot provide a high level of radioprotective action for large animals, but it may promote recovery.

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Section: Reviewmentioning

confidence: 99%

Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals

Ушаков

2014

Journal of Radiation Research

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“…As a direct alpha1-adrenomimetic, indralin causes changes in microcirculation due to the vasoconstriction of pre-capillaries and the simultaneous increase in oxygen consumption by cells through the stimulation of tissue respiration [21, 23–25]. The respiration of 100% oxygen during irradiation decreases the radioprotective effects of indralin [23, 24].…”

Section: Discussionmentioning

confidence: 99%

“…These outcomes promote the development of acute circulatory and tissue hypoxia, e.g. in the haematopoietic tissues of large animal such as dogs [24, 25]. The radioprotective efficacy of indralin on haematopoiesis is first of all implemented by the protection of haematopoietic stem cells in the bone marrow and spleen.…”

Section: Introductionmentioning

confidence: 99%

Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

Semenov

Суворов²,

Antipov

et al. 2014

Journal of Radiation Research

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The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2–3-years-old and weighing 2.1–3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40–120 mg kg–1) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg–1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3–94.3) mg kg–1, and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg–1. Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys.

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“…A high radioprotective efficiency of indralin in the large animals (dogs, monkeys) (Vasin et al 1997b, 2014a) is largely predetermined, in addition to the vasoconstrictive effect, by its ability as a α 1 -adrenomimetic to stimulate the oxygen consumption in hematopoietic tissues (Vasin et al 2013) thus inducing acute cellular hypoxia (Vasin et al 1997a, 1999). …”

Section: Reviewmentioning

confidence: 99%

Comments on the mechanisms of action of radiation protective agents: basis components and their polyvalence

Vasin

2014

SpringerPlus

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PurposeThese comments suggest a division of radiation protective agents on the grounds of their mechanism of action that increase the radio resistance of an organism.ConclusionGiven below is the division of radiation protective agents on the basis of their mechanism of action into 3 groups: 1) Radiation protective agents, with the implementation of radiation protective action taking place at the cellular level in the course of rapidly proceeding radiation-chemical reactions. At the same time, when the ionizing radiation energy is absorbed, these agents partially neutralize the “oxygen effect” as a radiobiological phenomenon, especially in the radiolysis of DNA; 2) Radiation protective agents that exert their effect at the system level by accelerating the post-radiation recovery of radiosensitive tissues through activation of a number of pro-inflammatory signaling pathways and an increase in the secretion of hematopoietic growth factors, including their use as mitigators in the early period after irradiation prior to the clinical development of acute radiation syndrome (ARS). 3) Radiomodulators including drugs and nutritional supplements that can elevate the resistance of the organism to adverse environmental factors, including exposure to ionization by means of modulating the gene expression through a hormetic effect of small doses of stressors and a “substrate” maintenance of adaptive changes, resulting in an increased antioxidant protection of the organism. Radiation protective agents having polyvalence in implementation of their action may simultaneously induce radioprotective effect by various routes with a prevalence of basis mechanisms of the action.

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Effect of α1-Adrenomimetic Indralin on Oxygen Consumption by Bone Marrow Cells in Vitro

Cited by 6 publications

References 2 publications

Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals

Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals

Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

Comments on the mechanisms of action of radiation protective agents: basis components and their polyvalence

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