Mitigation of Ionizing Radiation-Induced Gastrointestinal Damage by Insulin-Like Growth Factor-1 in Mice

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F23%3A00558176" target="_blank" >RIV/60162694:G44__/23:00558176 - isvavai.cz</a>

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fphar.2022.663855/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fphar.2022.663855/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2022.663855" target="_blank" >10.3389/fphar.2022.663855</a>

Result language

angličtina

Original language name

Mitigation of Ionizing Radiation-Induced Gastrointestinal Damage by Insulin-Like Growth Factor-1 in Mice

Original language description

Purpose: Insulin-like growth factor-1 (IGF-1) stimulates epithelial regeneration but may also induce life-threatening hypoglycemia. In our study, we first assessed its safety. Subsequently, we examined the effect of IGF-1 administered in different dose regimens on gastrointestinal damage induced by high doses of gamma radiation. Material and methods: First, fasting C57BL/6 mice were injected subcutaneously with IGF-1 at a single dose of 0, 0.2, 1, and 2 mg/kg to determine the maximum tolerated dose (MTD). The glycemic effect of MTD (1 mg/kg) was additionally tested in non-fasting animals. Subsequently, a survival experiment was performed. Animals were irradiated (Co; 14, 14.5, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously at 1 mg/kg 1, 24, and 48 h after irradiation. Simultaneously, mice were irradiated (Co; 12, 14, or 15 Gy; shielded head), and IGF-1 was administered subcutaneously under the same regimen. Jejunum and lung damage were assessed 84 h after irradiation. Finally, we evaluated the effect of six different IGF-1 dosage regimens administered subcutaneously on gastrointestinal damage and peripheral blood changes in mice 6 days after irradiation (Co; 12 and 14 Gy; shielded head). The regimens differed in the number of doses (one to five doses) and the onset of administration (starting at 1 [five regimens] or 24 h [one regimen] after irradiation). Results: MTD was established at 1 mg/kg. MTD mitigated lethality induced by 14 Gy and reduced jejunum and lung damage caused by 12 and 14 Gy. However, different dosing regimens showed different efficacy, with three and four doses (administered 1, 24, and 48 h and 1, 24, 48, and 72 h after irradiation, respectively) being the most effective. The three-dose regimens supported intestinal regeneration even if the administration started at 24 h after irradiation, but its potency decreased. Conclusion: IGF-1 seems promising in the mitigation of high-dose irradiation damage. However, the selected dosage regimen affects its efficacy.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

1663-9812

Volume of the periodical

13

Issue of the periodical within the volume

June

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

663855

UT code for WoS article

000826513000001

EID of the result in the Scopus database

2-s2.0-85134152651