Protective Action of 2,4-dinitrophenol against X-radiation Injury

Praslìcka, M; Hill, M.; Novák, L

doi:10.1080/09553006214550381

Cited by 5 publications

(3 citation statements)

References 23 publications

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“…The increase in cell radioresistance owing to acute low oxygen tension is a result of the considerable increase in cellular oxygen consumption previously discussed [ 64 , 109 ]. The radioprotective effect of uncouplers of oxidative phosphorylation confirms such a possibility [ 110 – 112 ].…”

Section: Reviewmentioning

confidence: 78%

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: 78%

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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“…Extensive uncoupling of oxidative phosphorylation with sharp oxygen consumption in cells induces to the development of acute cellular hypoxia that is key factor for an implementation of high radioprotective effect. This fact was confirmed by the administration of uncoupler of oxidative phosphorylation 2,4-dinitriphenol when it was detected 100% protective effect (Praslicka et al 1962; Vacek and Rotkovska 1964). …”

Section: Reviewmentioning

confidence: 83%

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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“…Finally, investigators demonstrated an awareness of differential radiation sensitivities among organs, although, as mentioned previously, only a few of the journal's articles focused on specific tissues versus whole body responses. Those that looked beyond survival had examined protection in the more radiation-sensitive tissues, such as bone marrow (Weiss 1961;Praslicka et al 1962), gut/ mucosa and testes (Mandl 1959;Ashwood-Smith 1961;Starkie 1961), suggesting a continued focus on the acute radiation response and its associated syndromes.…”

Section: Kickmentioning

confidence: 99%

Saving normal tissues – a goal for the ages

Groves

Williams

2019

International Journal of Radiation Biology

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Purpose: Almost since the earliest utilization of ionizing radiation, many within the radiation community have worked towards either preventing (i.e. protecting) normal tissues from unwanted radiation injury or rescuing them from the downstream consequences of exposure. However, despite over a century of such investigations, only incremental gains have been made towards this goal and, with certainty, no outright panacea having been found. In celebration of the 60 th anniversary of the International Journal of Radiation Biology and to chronicle the efforts that have been made to date, we undertook a non-rigorous survey of the articles published by normal tissue researchers in this area, using those that have appeared in the aforementioned journal as a road map. Three 'snapshots' of publications on normal tissue countermeasures were taken: the earliest (1959-1963) and most recent (2013-2018) 5-years of issues, as well as a 5-year intermediate span (1987-1991). Conclusions: Limiting the survey solely to articles appearing within International Journal of Radiation Biology likely reduced the number of translational studies interrogated given the basic science tenor of this particular publication. In addition, by taking 'snapshots' rather than considering the entire breadth of the journal's history in this field, important papers that were published during the interim periods were omitted, for which we apologize. Nonetheless, since the journal's inception, we observed that, during the chosen periods, the majority of studies undertaken in the field of normal tissue countermeasures, whether investigating radiation protectants, mitigators or treatments, have focused on agents that interfere with the physical, chemical and/or biological effects known to occur during the acute period following whole body/ high single dose exposures. This relatively narrow approach to the reduction of normal tissue effects, especially those that can take months, if not years, to develop, seems to contradict our growing understanding of the progressive complexities of the microenvironmental disruption that follows the initial radiation injury. Given the analytical tools now at our disposal and the enormous benefits that may be reaped in terms of improving patient outcomes, as well as the potential for

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Protective Action of 2,4-dinitrophenol against X-radiation Injury

Cited by 5 publications

References 23 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

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

Saving normal tissues – a goal for the ages

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