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 - 2020/3
Y1 - 2020/3
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[rad] 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[rad] 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
C2 - 31494145
SN - 0006-2952
SP - 113631
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -
