Pharmacological properties of selenium and its preparations: from antioxidant to neuroprotector

Abstract

Selenium is an essential component of more than two dozen enzymes and other selenoproteins that play critical roles in reproduction, DNA synthesis, thyroid hormone metabolism, and protection from oxidative damage and infection. Selenium has a protective action against some forms of cancer and cardiovascular diseases, modulates levels of inflammatory mediators, promotes to maintain bone homeostasis and protects against bone loss. Selenium significance as a cardioprotective agent may be associated not only with its antioxidant properties, but also with its ability to prevent inflammation, autophagy, as well as the intrinsic and extrinsic apoptosis pathways. Signaling pathways, such as p-AMPK, PARP, Nrf2, STAT, are involved in the protective effects of selenium. Selenium protects against cardiovascular damage by increasing the survival rate of cardiomyocytes, including a mitochondria-dependent pathway and autophagy through peroxisome proliferator-activated receptors. Research demonstrating neuroprotective and cardioprotective effects of selenium preparations – selenoline, selenocysteine and selenomethionine – is growing at a rapid rate. It has been established that these compounds are able to normalize the levels of heat shock proteins (HSP70), which limit the cytotoxic effects of free radicals, produce energotropic action, prevent a decrease in the membrane mitochondria charge, and the opening of the mitochondrial pore. Also regulate the expression of transmembrane factors NF-kB, c-fos, which is associated with their main biological function of chaperone proteins, providing protection of neurons from damage. In this review, we want to emphasize pharmacological role of Selenium and its derivatives on human health is very complex and has yet to be fully understood.

Nitric oxide-dependent mechanism of endothelial dysfunction formation is a promising target link for pharmacological management

“…The main mechanism for the formation of endothelial dysfunction is a decrease in the formation and bioavailability of NO, the appearance of its cytotoxic forms against the background of oxidative stress and a deficiency of low molecular weight reduced thiols [6,8,12,13]. At the same time, the main reasons for NO deficiency in endothelial cells can be a reduced content of the precursor of nitric oxide L-arginine, a decrease in the ex-pression or activity of endothelial NO synthase, a lack of cofactors for NO synthesis (especially tetrahydrobiopterin), increased levels of endogenous eNOS inhibitors asymmetric dimethylarginine and monomethyl-Larginine, an increased production of reactive oxygen species (in particular, superoxide anion), as well as low density lipoproteins (especially their oxidized forms) [6,8,12].…”

“…It is well known that these heterocyclic derivatives have a wide spectrum of biological activity which makes them promising in search for new drugs [11,12]. Lately, the effects of 1,2,4-triazole derivatives on the vascular endothelium, myocardium and the brain have been studied; and the cardio-, endotheliumand neuroprotective properties have been discovered [9,10,12,13].…”

“…With ED, a deficiency of NO is recorded, and as a result, a decrease in its vasodilating properties due to the transformation into cytotoxic forms. All this determines the creation of molecules-modulators of the NO system as potential endothelioprotectors [4,5,8,13].…”

Endothelial dysfunction: developmental mechanisms and therapeutic strategies

“…Polyunsaturated fatty acids, antioxidants, vitamins (especially, tocopherol and ascorbic acid), folic acid, and L-arginine have been found to have a beneficial effect on vascular endothelial function (Konovalova et al 2019;Belenichev et al 2021). They improve endothelium-dependent vasodilation both in patients at high risk of cardiovascular diseases and in healthy people without risk factors (Brownand Hu 2001;Kurtz et al 2018).…”

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“…The molecular basis of vascular endothelial dysfunction is a complex and not fully understood problem. In this regard, the system "endothelial NOS-synthase-L-arginine-NO" can be certainly claimed as the leading link for the pharmacological management of endothelial dysfunction in the near future [6,13].…”