5-hydroxytryptamine as a Radiation Protective Substance in Animals

Langendorff, H.; Melching, H.; Ladner, H.-A.

doi:10.1080/09553005914550051

Cited by 22 publications

(2 citation statements)

References 3 publications

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“…For example, a decrease in the tryptophan and histidine metabolism, including tryptophan, serotonin, and histamine values, was reported in studies using mouse serum, mouse intestine, and rat urine [25][26][27][28][29]. These metabolites were reported to function as radioprotectors [30][31][32], and we observed that a decrease in these radioprotective metabolites helped explain the radiation-induced damage. We also observed a decrease in the components of the pyrimidine metabolism pathway, such as thymidine, in TBI mice, although several previous studies using mouse serum and urine showed that TBI upregulated the levels of thymidine, reflecting DNA or RNA damage [26,33].…”

Section: Discussionsupporting

confidence: 65%

An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice

2022

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The thrombopoietin receptor agonist romiplostim (RP) was recently approved by the US Food and Drug Administration for improving survival in patients acutely exposed to myelosuppressive doses of radiation. Our previous studies with mice have shown that RP administration after lethal irradiation not only completely rescues irradiated mice but also shows mitigative effects on their hematopoiesis and multiple organ injury, including that of the lung, bone marrow, small intestine, and liver. However, the mechanism by which RP functions as a radiomitigator remains unclear. In the present study, we applied a metabolomics approach, which has the ability to reflect the status of an organism directly and accurately, helping to elucidate the biology of treatment responses. Our results showed that the disruption of several metabolites and pathways in response to total body irradiation was partially corrected by RP administration. Notably, RP-corrected metabolites and pathways have been reported to be indicators of DNA damage and lung, bone marrow, small intestine, and liver injury. Taken together, the present findings suggested that the radiomitigative effect of RP is partially involved in the recovery of organ injury, and the identified metabolites may be a useful biomarker of the survival likelihood following radiation exposure.

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Section: Discussionsupporting

confidence: 65%

An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice

2022

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“…Of the above-mentioned compounds, serotonin had the highest radioprotective effect, comparable with that of cystamine [ 14 – 16 ]. Later , similar protective properties were found in 5-methyl derivatives of serotonin—e.g.…”

Section: Introductionmentioning

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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Some aspects of the effects of radiations on the metabolism of tissues and tumours

Mitchell¹

1966

Handbuch Der Medizinischen Radiologie / Encyclopedia of Medical Radiology

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5-hydroxytryptamine as a Radiation Protective Substance in Animals

Cited by 22 publications

References 3 publications

An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice

An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice

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

Some aspects of the effects of radiations on the metabolism of tissues and tumours

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