Genotoxic and genoprotective effects of 1,4-dihydropyridine derivatives: a brief review

Elina Leonova University of Latvia Faculty of Medicine, Medical Biochemistry Department, Riga, Latvia
Nadezhda Ryabokon National Academy of Sciences of Belarus, Institute of Genetics and Cytology, Minsk, Belarus
Evita Rostoka University of Latvia Faculty of Medicine, Medical Biochemistry Department, Riga, Latvia
Vitalijs Borisovs University of Latvia Faculty of Medicine, Medical Biochemistry Department, Riga, Latvia
Astrida Velēna Latvian Institute of Organic Synthesis, Riga, Latvia
Egils Bisenieks Latvian Institute of Organic Synthesis, Riga, Latvia
Gunars Duburs Latvian Institute of Organic Synthesis, Riga, Latvia
Maija Dzintare Latvian Academy of Sport Education, Department of Anatomy, Physiology, Biochemistry, Biomechanics, Hygiene and Informatics, Riga, Latvia
Roza Goncharova National Academy of Sciences of Belarus, Institute of Genetics and Cytology, Minsk, Belarus
Nikolajs Sjakste Latvian Institute of Organic Synthesis

DOI: https://doi.org/10.2478/aiht-2023-74-3707

Keywords: 1,4-DHP, AV-153, diludine, DNA binding, carbatones, glutapyrone

Abstract

This review summarises current knowledge about the genotoxic and genoprotective effects of 1,4-dihydropyridines (DHP) with the main focus on the water-soluble 1,4-DHPs. Most of these water-soluble compounds manifest very low calcium channel blocking activity, which is considered "unusual" for 1,4-DHPs. Glutapyrone, diludine, and AV-153 decrease spontaneous mutagenesis and frequency of mutations induced by chemical mutagens. AV-153, glutapyrone, and carbatones protect DNA against the damage produced by hydrogen peroxide, radiation, and peroxynitrite. The ability of these molecules to bind to the DNA may not be the only mechanism of DNA protection, as other mechanisms such as radical scavenging or binding to other genotoxic compounds may take place and enhance DNA repair. These uncertainties and reports of high 1,4-DHP concentrations damaging the DNA call for further in vitro and in vivo preclinical research, pharmacokinetic in particular, as it can help pinpoint the exact mechanism(s) of the genotoxic and/or genoprotective action of 1,4-DHPs.

Published

2023-03-20

How to Cite

Leonova E, Ryabokon N, Rostoka E, Borisovs V, Velēna A, Bisenieks E, Duburs G, Dzintare M, Goncharova R, Sjakste N. Genotoxic and genoprotective effects of 1,4-dihydropyridine derivatives: a brief review. Arh Hig Rada Toksikol [Internet]. 2023Mar.20 [cited 2024Apr.25];74(1). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/1557