Effect of Melatonin, Ascorbic Acid, and Succinic Acid on the Cumulative Toxic Effect of Repeated Treatment with Gammafos (Amifostine)

Ушаков, И. Б.; Kovtun, V. Yu.; Komarova, S. N.; Семенова, Л. А.

doi:10.1023/b:bebm.0000038150.18659.3b

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…One might expect aggravation of the above situation in dogs as a result of the slower metabolism of aminothiols in irradiated animals. Accumulation of the toxic effects of aminothiols decreases their radioprotective action [ 71 – 73 ]. The increase in the radioprotective effectiveness of cystamine with increasing drug dosage is limited by the maximum tolerated dose [ 49 ], which does not exceed the ED50 in dogs [ 66 , 74 ].…”

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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“…In addition, melatonin is described as the prevention of breast radiation dermatitis [98]. Topical applications of melatonin emulsions to the management of skin toxicity during radiotherapy have been proposed [99]. In this sense, A phase II, prospective, double-blind randomized trial was designed to evaluate the efficacy of melatonin-containing cream (twice daily) in breast cancer patients during radiation treatment.…”

Section: Clinical Trials and Possible Applications Of Melatonin In Br...mentioning

confidence: 99%

A Promising Challenge in the Link between Melatonin and Breast Cancer: Exploring the Microbiome-Gut-Brain Axis

González-González¹,

Laborda-Illanes²,

Boutriq³

et al. 2022

Melatonin - Recent Updates

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In this chapter, we describe the possible link between gut microbiota, melatonin, and breast cancer disease. It is widely described that changes in melatonin production due to circadian disruption is one of the causes of breast cancer. In addition, recently it is described that dysbiosis caused by changes in the gut microbiota composition could be as well constitute an important factor to induce breast cancer. The dysbiosis process, in turn, induces the stimulation of kynurenine pathway, leading to reduced circulating melatonin levels. Therefore, in this chapter we deep into the relationship between circadian disruption, dysbiosis, and breast cancer disease. This constitutes an important step in the therapeutic approach and prevention of this pathology.

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“…However, long time everyday administration of aminothiols in high doses causes decrease of their protective efficacy through the cumulation of their cytostatic or cytotoxic effects inhibited early post-radiation reparation of radiosensitive tissues (Travis et al 1988; Coia and Brown 1989; Vasin et al 1991, Vasin et al 2004b). …”

Section: Reviewmentioning

confidence: 99%

“…Antioxidants (quercetin, vitamins A and C, beta-carotene, selenium, melatonin, and glutathione) can be used in clinical practice for the decrease of the toxicity of radio-chemotherapy for cancer patients (Lamson and Brignall 2000, Vasin et al 2004a, 2004b). …”

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 Melatonin, Ascorbic Acid, and Succinic Acid on the Cumulative Toxic Effect of Repeated Treatment with Gammafos (Amifostine)

Cited by 9 publications

References 6 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

A Promising Challenge in the Link between Melatonin and Breast Cancer: Exploring the Microbiome-Gut-Brain Axis

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

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