Novel organoselenium catalysts : from the heart of tuna fish to antioxidant capacity linked with nitric oxide signaling in cardiovascular diseases (SeleNOx)

Abstract

Novel organoselenium catalysts: From the heart of tuna fish to antioxidant capacity linked with nitric oxide signaling in cardiovascular diseases (SeleNOx) Cardiovascular diseases are often linked to oxidative stress and reduced bioavailability of nitric oxide (●NO), leading to disruption of vascular homeostasis. Certain small, stable organoselenium molecules display antioxidant activity similar to that of glutathione peroxidase (GPx), as well as the ability to catalyse the release of ●NO from S-nitrosothiols (RSNOs). They can be of synthetic origin, such as ebselen, or natural, such as selenonein found in tuna. This study proposes the synthesis and evaluation in tubo, in vitro on human aortic smooth muscle cells (HuAoSMC) and ex vivo on isolated rat aortic rings, of new selenohydantoins inspired by selenonein. In tubo selenohydantoins 5e (with -CF3 substitution) and 5d (with -CH3 substitution) exhibited antioxidant, GPx-like activity and catalytic activity stimulating ●NO release from S-nitrosoglutathione (GSNO) greater than ebselen and selenocysteamine respectively. Selenohydantoins were shown to be cytocompatible with HuAoSMC, and 5e proved to be the best catalyst for ●NO release from GSNO, significantly increasing the intracellular pool of ●NO formed from nitrite ions and S-nitrosothiols, without affecting cellular redox balance (GPx activity and intracellular glutathione concentration). Finally, 5e and 5f were shown to mobilize ●NO stored in the aorta in the form of S-nitrosothiols, inducing vasorelaxation of precontracted rat aortic rings. The results of this study suggest potential applications of synthesized selenohydantoins in the cardiovascular field, particularly in pathological conditions characterized by oxidative stress and impaired endothelial function. key words: Selenium, Nitric oxide, S-nitrosation, Endothel, Vasorelaxation.