Modifying action of metformin on the cytogenetic effects of doxorubicin and cyclophosphamide in mice
- Authors: Zhanataev A.K.1, Kulakova A.V.1, Durnev A.D.1
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Affiliations:
- Research Zakusov Institute of Pharmacology
- Issue: Vol 21, No 1 (2023)
- Pages: 53-60
- Section: Genetic toxicology
- URL: https://journals.rcsi.science/ecolgenet/article/view/132249
- DOI: https://doi.org/10.17816/ecogen133621
- ID: 132249
Cite item
Abstract
BACKGROUND: The causal relationship between mutagenesis and carcinogenesis is well known. Hence the wide interest in the study of the mutagen-modifying effects of natural and synthetic compounds. Particular attention is drawn to widespread compounds. One of them, metformin, is widely used as a hypoglycemic drug.
AIM: evaluation of the influence of metformin on the cytogenetic effects of doxorubicin and cyclophosphamide in mouse bone marrow cells.
MATERIALS AND METHODS: Male F1 CBAxC57Bl/6 hybrid mice were used. Cyclophosphamide (20 mg/kg) or doxorubicin (10 mg/kg) was administered intraperitoneally, metformin was given orally once or for 4 consecutive days. The latter administration of metformin was combined with mutagen administration. Cytogenetic preparations of bone marrow cells were prepared 18 hours after metformin administration and 24 hours after its combined administration with mutagens. Chromosomal aberrations were analyzed according to accepted protocols.
RESULTS: Metformin per se showed no cytogenetic activity at doses of 500, 1000, and 2000 mg/kg. At a dose of 500 mg/kg, but not 100 or 250 mg/kg, metformin reduced the cytogenetic effects of doxorubicin. Metformin administered once and for 4 days at doses of 100, 250, and 500 mg/kg or once at doses of 10 and 20 mg/kg increased the number of metaphases with chromosome aberrations induced by cyclophosphamide by a factor of 2 to 3. At doses of 2.5 and 5 mg/kg, metformin had no modifying effect on the mutagen effect.
CONCLUSION: Metformin attenuates the cytogenetic effects of doxorubicin and enhances the cytogenetic activity of cyclophosphamide in mouse bone marrow cells. This allows us to conclude that metformin has mutagen-modifying properties.
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##article.viewOnOriginalSite##About the authors
Aliy K. Zhanataev
Research Zakusov Institute of Pharmacology
Author for correspondence.
Email: zhanataev@academpharm.ru
ORCID iD: 0000-0002-7673-8672
SPIN-code: 7070-0510
Cand. Sci. (Biol.), leading research associate of the Laboratory of Mutagenesis Pharmacology of Department of Drug Toxicology
Russian Federation, MoscowAlla V. Kulakova
Research Zakusov Institute of Pharmacology
Email: allakulak@mail.ru
ORCID iD: 0000-0002-6959-2150
Scopus Author ID: 7006681153
Cand. Sci. (Biol.), senior research associate of the Laboratory of Mutagenesis Pharmacology of Drug Toxicology Department
Russian Federation, MoscowAndrey D. Durnev
Research Zakusov Institute of Pharmacology
Email: addurnev@mail.ru
ORCID iD: 0000-0003-0218-8580
SPIN-code: 8426-0380
Scopus Author ID: 7006060753
Dr. Sci. (Med.), professor, corresponding member of RAS; head of the Department of Drug Toxicology and Pharmacology of Mutagenesis
Russian Federation, MoscowReferences
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