A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice

Cheda, Aneta; Nowosielska, Ewa M.; Gębicki, Jerzy; Marcinek, Andrzej; Chłopicki, Stefan; Janiak, Marek K.

doi:10.1038/s41598-021-86870-3

Cited by 4 publications

(4 citation statements)

References 45 publications

(28 reference statements)

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“…These prosurvival effects might be related to the anti-inflammatory and/or antithrombotic properties of the vitamin B3 derivatives and do not seem to be mediated by stimulation of hematopoiesis. These results show that MNA may represent a prototype of a radiomitigator because it reduces the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of IR [184].…”

Section: Vitaminsmentioning

confidence: 78%

Radioprotectors, Radiomitigators, and Radiosensitizers

Montoro,

Obrador,

Mistry

et al. 2023

Radiobiology Textbook

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This chapter gives an overview of molecules and mechanisms able to intervene with the biological effects of ionizing radiation (IR), either related to their clinical use in radiotherapy or in the field of radiation protection in case of an accidental exposure to radiation and/or nuclear emergencies. According to the National Cancer Institute, “radiomodifiers” can be classified into (a) radioprotectors (protect molecules and tissues from direct and indirect damage induced by IR) or (b) radiomitigators (reduce and help to repair damage), depending on whether they are administered pre- or post-IR exposure, respectively. Most of them are free radical scavengers and antioxidants (or enhancers of the antioxidant defenses), increase DNA repair mechanisms, have anti-inflammatory properties, and/or prevent cell death. On the other hand, (c) radiosensitizers directly or indirectly enhance DNA damage and ROS production, increasing IR toxicity on tumor cells, thus they are used to increase radiotherapy efficacy in cancer patients. The section “Radionuclides and methods to treat contaminated individuals” describes the medical consequences and treatment modalities of internal contamination by radionuclides. Overall, the chapter discusses the effects of most currently known radiomodifiers, their specific properties, and their mechanisms of action, by emphasizing results obtained in recent preclinical and clinical trials.

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Section: Vitaminsmentioning

confidence: 78%

Radioprotectors, Radiomitigators, and Radiosensitizers

Montoro,

Obrador,

Mistry

et al. 2023

Radiobiology Textbook

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“…We identified specific metabolites and pathways associated with recurrent participants, non-recurrent participants, or both.The metabolites identified in the non-recurrent patients include: methylnicotinamide, a metabolite of the class of nicotinamides (NAD + ) and most species, including humans and Plasmodium can produce NAD + 35 , 36 . Previous studies on Plasmodium species reported high NAD + levels during malaria, with infected erythrocytes having 5 to tenfold higher concentrations compared to the uninfected red blood cells 31 , 32 . In a malaria challenge study, methylnicotinamide was demonstrated to be of variable importance upon P. falciparum infection, being significantly higher among the Europeans than the Africans 37 .…”

Section: Discussionmentioning

confidence: 89%

“…In addition, we observed that the abundance of diamino-hydroxy-methylformamidopyrimidine was reduced with significant difference at D90 compared to D0, during the active vivax malaria, before the treatment. Almost all the metabolites annotated were either amino acids or their intermediates except methylnicotinamide which is a form of vitamin B3 31 (Fig. 2 a).…”

Section: Resultsmentioning

confidence: 99%

Host metabolomic responses in recurrent P. vivax malaria

Yakubu,

Mwangi,

Netto

et al. 2024

Sci Rep

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Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC–MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups. Overall, 51 recurrent and 59 non-recurrent patients were included in the study. Longitudinal metabolomic analysis revealed 52 and 37 significant metabolite features from the recurrent and non-recurrent participants, respectively. Recurrence was associated with disturbances in eicosanoid metabolism. Comparison between groups suggest alterations in vitamin B6 (pyridoxine) metabolism, tyrosine metabolism, 3-oxo-10-octadecatrienoate β-oxidation, and alkaloid biosynthesis II. Integrative network analysis revealed enrichment of other metabolic pathways for the recurrent phenotype, including the butanoate metabolism, aspartate and asparagine metabolism, and N-glycan biosynthesis. The metabolites and metabolic pathways predicted in our study suggest potential biomarkers of recurrence and provide insights into targets for antimalarial development against P. vivax.

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“…Furthermore, these discrepancies in miRNA expression between the sensitive and resistant strains have potential to predict who is more likely to require urgent care vesus routine follow-up. Further, differences in relative resistance as determined by reported LD50/30 for each strain may explain the difficulty in differentiating miRNAs altered at 1 Gy, 2 Gy, 4 Gy (viable) vs. 8 Gy (high risk) but allow for differentiation between low dose (1 and 2 Gy) compared to high dose (4 Gy and 8 Gy) (66)(67)(68)(69). After a 4 Gy dose, BALB/c mice may already be succumbing to radiation injury, while C3H/HeJ and C57BL/6 are surviving.…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of miRNA Expression after Whole-Body Irradiation Across Three Strains of Mice

Martello,

Bylicky,

Shankavaram

et al. 2023

Radiation Research

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Whole- or partial-body exposure to ionizing radiation damages major organ systems, leading to dysfunction on both acute and chronic timescales. Radiation medical countermeasures can mitigate acute damages and may delay chronic effects when delivered within days after exposure. However, in the event of widespread radiation exposure, there will inevitably be scarce resources with limited countermeasures to distribute among the affected population. Radiation biodosimetry is necessary to separate exposed from unexposed victims and determine those who requires the most urgent care. Blood-based, microRNA signatures have great potential for biodosimetry, but the affected population in such a situation will be genetically heterogeneous and have varying miRNA responses to radiation. Thus, there is a need to understand differences in radiation-induced miRNA expression across different genetic backgrounds to develop a robust signature. We used inbred mouse strains C3H/HeJ and BALB/c mice to determine how accurate miRNA in blood would be in developing markers for radiation vs. no radiation, low dose (1 Gy, 2 Gy) vs. high dose (4 Gy, 8 Gy), and high risk (8 Gy) vs. low risk (1 Gy, 2 Gy, 4 Gy). Mice were exposed to whole-body doses of 0 Gy, 1 Gy, 2 Gy, 4 Gy, or 8 Gy of X rays. MiRNA expression changes were identified using NanoString nCounter panels on blood RNA collected 1, 2, 3 or 7 days postirradiation. Overall, C3H/HeJ mice had more differentially expressed miRNAs across all doses and timepoints than BALB/c mice. The highest amount of differential expression occurred at days 2 and 3 postirradiation for both strains. Comparison of C3H/HeJ and BALB/c expression profiles to those previously identified in C57BL/6 mice revealed 12 miRNAs that were commonly expressed across all three strains, only one of which, miR-340-5p, displayed a consistent regulation pattern in all three miRNA data. Notably multiple Let-7 family members predicted high-dose and high-risk radiation exposure (Let-7a, Let-7f, Let-7e, Let-7g, and Let-7d). KEGG pathway analysis demonstrated involvement of these predicted miRNAs in pathways related to: Fatty acid metabolism, Lysine degradation and FoxO signaling. These findings indicate differences in the miRNA response to radiation across various genetic backgrounds, and highlights key similarities, which we exploited to discover miRNAs that predict radiation exposure. Our study demonstrates the need and the utility of including multiple animal strains in developing and validating biodosimetry diagnostic signatures. From this data, we developed highly accurate miRNA signatures capable of predicting exposed and unexposed subjects within a genetically heterogeneous population as quickly as 24 h of exposure to radiation.

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A derivative of vitamin B3 applied several days after exposure reduces lethality of severely irradiated mice

Cited by 4 publications

References 45 publications

Radioprotectors, Radiomitigators, and Radiosensitizers

Radioprotectors, Radiomitigators, and Radiosensitizers

Host metabolomic responses in recurrent P. vivax malaria

Comparative Analysis of miRNA Expression after Whole-Body Irradiation Across Three Strains of Mice

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