Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Comparative Study of ROS Production and Cytotoxicity Induced by Combinations of Thiols with HOCbl and CNCbl

Version 1 : Received: 8 August 2022 / Approved: 11 August 2022 / Online: 11 August 2022 (06:17:50 CEST)

A peer-reviewed article of this Preprint also exists.

Shatalin, Y.V.; Shubina, V.S.; Solovieva, M.E.; Akatov, V.S. Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins. Int. J. Mol. Sci. 2022, 23, 11032. Shatalin, Y.V.; Shubina, V.S.; Solovieva, M.E.; Akatov, V.S. Differences in the Formation of Reactive Oxygen Species and Their Cytotoxicity between Thiols Combined with Aqua- and Cyanocobalamins. Int. J. Mol. Sci. 2022, 23, 11032.

Journal reference: Int. J. Mol. Sci. 2022, 23, 11032
DOI: 10.3390/ijms231911032

Abstract

Cobalamin is an essential nutrient required for the normal functioning of cells. Its deficiency can lead to various pathological states. Hydroxocobalamin (HOCbl) and cyanocobalamin (CNCbl) are the forms of vitamin B12 that are most commonly used for supplementation. There is substantial evidence indicating that cobalamins can both suppress and promote oxidative stress; however, the mechanisms underlying these effects are poorly understood. Here, it was shown that the oxidation of thiols catalyzed by HOCbl and CNCbl is accompanied by ROS production and induces, under certain conditions, oxidative stress and cell death. The form of vitamin B12 and the structure of thiol play a decisive role in these processes. It was found that the mechanisms and kinetics of thiol oxidation catalyzed by HOCbl and CNCbl differ substantially. It was discussed how these differences may explain different levels of ROS production and cytotoxicity induced by combinations of thiols with HOCbl and CNCbl. On the whole, the data obtained provide a new insight into the redox processes in which cobalamins are involved and might be helpful in developing new approaches to the treatment of some cobalamin-responsive disorders in which oxidative stress is an important component. In addition, these data may be useful for a better understanding of mechanisms underlying induction of different types of death of cancer cells and in a search for new targets for anticancer therapy.

Keywords

hydroxocobalamin; cyanocobalamin; thiolatocobalamins; thiol oxidation; ROS production; cytotoxicity

Subject

LIFE SCIENCES, Biochemistry

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