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

Aneta Cheda,Jerzy Gebicki,Stefan Chlopicki,Ewa M Nowosielska,Andrzej Marcinek,Marek K Janiak

doi:10.1038/s41598-021-86870-3

Aneta Cheda, Jerzy Gebicki + Show 4 more

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https://doi.org/10.1038/s41598-021-86870-3

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Abstract

Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. In the present study we demonstrate for the first time that 1-methyl nicotinamide (MNA), a derivative of vitamin B3, significantly (1.6 to 1.9 times) prolonged survival of BALB/c mice irradiated at LD30/30 (6.5 Gy), LD50/30 (7.0 Gy) or LD80/30 (7.5 Gy) of γ-rays when the MNA administration started as late as 7 days post irradiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B3 derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). These pro-survival effects did not seem to be mediated by stimulation of haematopoiesis, but might be related to anti-inflammatory and/or anti-thrombotic properties of the vitamin B3 derivatives. Our results show that MNA may represent a prototype of a radioremedial agent capable of mitigating the severity and/or progression of radiation-induced injuries when applied several hours or days after exposure to high doses of ionizing radiation.

Highlights

Most, if not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation
Methylnicotinamide; 1,3-MAP –1-methyl-3-acetylpyridine; Control—mice exposed to whole-body irradiation (WBI) at 6.5, 7.0, or
7.5 Gy γ-rays; 7th day pre-WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B 3 derivatives from the 7th day before WBI; day of WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B3 derivatives from the day of WBI; 7th day post-WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B3 derivatives from the 7th day after WBI. *Indicates statistically significant (p < 0.05) difference from the results obtained in the irradiated control group

Summary

Introduction

If not all, of the hitherto tested substances exert more or less pronounced pro-survival effects when applied before or immediately after the exposure to high doses of ionizing radiation. A slightly less efficient and only after the highest dose (7.5 Gy) of γ-rays was another vitamin B3 derivative, 1-methyl-3-acetylpyridine (1,3-MAP) (1.4-fold prolonged survival). Short-term exposures at such doses may result in acute radiation syndrome (ARS) and other pathologies whose underlying mechanisms include depression of proliferation of actively dividing progenitor cells, injury to the endothelial lining of blood vessels, inflammation, and thrombosis[1,2]. Such untoward effects could be prevented or alleviated by appropriate radiation countermeasures. 7.5 Gy γ-rays; 7th day pre-WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B 3 derivatives from the 7th day before WBI; day of WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B3 derivatives from the day of WBI; 7th day post-WBI—mice exposed to WBI at 6.5, 7.0, or 7.5 Gy γ-rays and fed the vitamin B3 derivatives from the 7th day after WBI. *Indicates statistically significant (p < 0.05) difference from the results obtained in the irradiated control group

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