Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings

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Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings. / Zacharias, Triantafyllos; Flouda, Konstantina; Jepps, Thomas A; Gammelgaard, Bente; Schiesser, Carl H; Davies, Michael J.

In: Biochemical Pharmacology, 05.09.2019, p. 113631.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Zacharias, T, Flouda, K, Jepps, TA, Gammelgaard, B, Schiesser, CH & Davies, MJ 2019, 'Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings', Biochemical Pharmacology, pp. 113631. https://doi.org/10.1016/j.bcp.2019.113631

APA

Zacharias, T., Flouda, K., Jepps, T. A., Gammelgaard, B., Schiesser, C. H., & Davies, M. J. (2019). Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings. Biochemical Pharmacology, 113631. https://doi.org/10.1016/j.bcp.2019.113631

Vancouver

Zacharias T, Flouda K, Jepps TA, Gammelgaard B, Schiesser CH, Davies MJ. Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings. Biochemical Pharmacology. 2019 Sep 5;113631. https://doi.org/10.1016/j.bcp.2019.113631

Author

Zacharias, Triantafyllos ; Flouda, Konstantina ; Jepps, Thomas A ; Gammelgaard, Bente ; Schiesser, Carl H ; Davies, Michael J. / Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings. In: Biochemical Pharmacology. 2019 ; pp. 113631.

Bibtex

@article{b106138985a8457f8c65cfbf48ffb29f,
title = "Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings",
abstract = "Chronic low-grade inflammation and oxidative damage are strongly associated with pathologies including cardiovascular disease. As a consequence, there is considerable interest in agents that mitigate damage. Selenium compounds can act as potent protective agents against oxidation due to the high reactivity and nucleophilicity of the selenium atom. 1,4-Anhydro-4-seleno-d-talitol (SeTal, a novel water-soluble selenium-based sugar) is a potent oxidant scavenger in vitro and in human plasma. Here we show that SeTal is highly stable in solutions that mimic biological fluids and the gastrointestinal tract, and is not rapidly degraded or metabolized unlike some other selenium-containing compounds. SeTal remains intact during extended storage, and it rapidly penetrates into, and effluxes from, primary human coronary artery endothelial and smooth muscle cells, but does not induce loss of metabolic activity, or modulate cell survival and growth rates at concentrations ≤2 mM. Steady-state intracellular concentrations can reach 2-10 μM. SeTal affords protection against H2O2- and HOCl-mediated oxidative damage, with this being independent of the concentration or activities of the selenium-dependent protective enzymes TrxR and GPx. Protection was observed with both concurrent drug and oxidant administration and also (to a lesser extent) with cellular pre-loading. SeTal also affords protection to isolated arterial segments, with the compound decreasing HOCl (50 μΜ) mediated effects on aortic ring relaxation, consistent with the preservation of NO bioavailability. The stability, bioavailability and protective actions of this compound, suggest that it is worthy of further investigation as a protective agent, particularly in the area of cardiovascular disease.",
author = "Triantafyllos Zacharias and Konstantina Flouda and Jepps, {Thomas A} and Bente Gammelgaard and Schiesser, {Carl H} and Davies, {Michael J}",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "9",
day = "5",
doi = "10.1016/j.bcp.2019.113631",
language = "English",
pages = "113631",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings

AU - Zacharias, Triantafyllos

AU - Flouda, Konstantina

AU - Jepps, Thomas A

AU - Gammelgaard, Bente

AU - Schiesser, Carl H

AU - Davies, Michael J

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/9/5

Y1 - 2019/9/5

N2 - Chronic low-grade inflammation and oxidative damage are strongly associated with pathologies including cardiovascular disease. As a consequence, there is considerable interest in agents that mitigate damage. Selenium compounds can act as potent protective agents against oxidation due to the high reactivity and nucleophilicity of the selenium atom. 1,4-Anhydro-4-seleno-d-talitol (SeTal, a novel water-soluble selenium-based sugar) is a potent oxidant scavenger in vitro and in human plasma. Here we show that SeTal is highly stable in solutions that mimic biological fluids and the gastrointestinal tract, and is not rapidly degraded or metabolized unlike some other selenium-containing compounds. SeTal remains intact during extended storage, and it rapidly penetrates into, and effluxes from, primary human coronary artery endothelial and smooth muscle cells, but does not induce loss of metabolic activity, or modulate cell survival and growth rates at concentrations ≤2 mM. Steady-state intracellular concentrations can reach 2-10 μM. SeTal affords protection against H2O2- and HOCl-mediated oxidative damage, with this being independent of the concentration or activities of the selenium-dependent protective enzymes TrxR and GPx. Protection was observed with both concurrent drug and oxidant administration and also (to a lesser extent) with cellular pre-loading. SeTal also affords protection to isolated arterial segments, with the compound decreasing HOCl (50 μΜ) mediated effects on aortic ring relaxation, consistent with the preservation of NO bioavailability. The stability, bioavailability and protective actions of this compound, suggest that it is worthy of further investigation as a protective agent, particularly in the area of cardiovascular disease.

AB - Chronic low-grade inflammation and oxidative damage are strongly associated with pathologies including cardiovascular disease. As a consequence, there is considerable interest in agents that mitigate damage. Selenium compounds can act as potent protective agents against oxidation due to the high reactivity and nucleophilicity of the selenium atom. 1,4-Anhydro-4-seleno-d-talitol (SeTal, a novel water-soluble selenium-based sugar) is a potent oxidant scavenger in vitro and in human plasma. Here we show that SeTal is highly stable in solutions that mimic biological fluids and the gastrointestinal tract, and is not rapidly degraded or metabolized unlike some other selenium-containing compounds. SeTal remains intact during extended storage, and it rapidly penetrates into, and effluxes from, primary human coronary artery endothelial and smooth muscle cells, but does not induce loss of metabolic activity, or modulate cell survival and growth rates at concentrations ≤2 mM. Steady-state intracellular concentrations can reach 2-10 μM. SeTal affords protection against H2O2- and HOCl-mediated oxidative damage, with this being independent of the concentration or activities of the selenium-dependent protective enzymes TrxR and GPx. Protection was observed with both concurrent drug and oxidant administration and also (to a lesser extent) with cellular pre-loading. SeTal also affords protection to isolated arterial segments, with the compound decreasing HOCl (50 μΜ) mediated effects on aortic ring relaxation, consistent with the preservation of NO bioavailability. The stability, bioavailability and protective actions of this compound, suggest that it is worthy of further investigation as a protective agent, particularly in the area of cardiovascular disease.

U2 - 10.1016/j.bcp.2019.113631

DO - 10.1016/j.bcp.2019.113631

M3 - Journal article

SP - 113631

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

ER -

ID: 228455391