https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(00)02490-9.pdf

The importance of selenium to human health

The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

The importance of selenium to human health.

The organoselenium and organotellurium compounds have been described as promising pharmacological agents in view of their unique biological properties. Glutathione peroxidase mimic, antioxidant activity and thioredoxin reductase inhibition are some of the properties reviewed here. On the other hand, little is known about the molecular toxicological effects of organoselenium and organotellurium compounds. Most of our knowledge arose from research on inorganic selenium and tellurium. However, the ability to oxidize sulfhydryl groups from biological molecules can be involved both in their pharmacological properties and in their toxicological effects. In fact, exposition to high doses of organoselenium or to low doses of organotellurium causes the depletion of endogenous reduced glutathione in a variety of tissues. Thus, the design of compounds that cause low depletion of glutathione and react with specific targeted proteins, controlling specific metabolic pathways, will represent an important progress in understanding the field of organochalcogen compounds. Furthermore, the development of new organochalcogens with higher thiol-peroxidase activity that can use other non-toxic thiol reducing agents, such as N-acetylcysteine instead of glutathione, will permit the investigation of the co-administration of organochalcogens and thiols as a formulation for antioxidant therapy.

Organoselenium and Organotellurium Compounds: Toxicology and Pharmacology

Although vitamin E has been known as an essential nutrient for reproduction since 1922, we are far from understanding the mechanisms of its physiological functions. Vitamin E is the term for a group of tocopherols and tocotrienols, of which alpha-tocopherol has the highest biological activity. Due to the potent antioxidant properties of tocopherols, the impact of alpha-tocopherol in the prevention of chronic diseases believed to be associated with oxidative stress has often been studied, and beneficial effects have been demonstrated. Recent observations that the alpha-tocopherol transfer protein in the liver specifically sorts out RRR-alpha-tocopherol from all incoming tocopherols for incorporation into plasma lipoproteins, and that alpha-tocopherol has signaling functions in vascular smooth muscle cells that cannot be exerted by other forms of tocopherol with similar antioxidative properties, have raised interest in the roles of vitamin E beyond its antioxidative function. Also, gamma-tocopherol might have functions apart from being an antioxidant. It is a nucleophile able to trap electrophilic mutagens in lipophilic compartments and generates a metabolite that facilitates natriuresis. The metabolism of vitamin E is equally unclear. Excess alpha-tocopherol is converted into alpha-CEHC and excreted in the urine. Other tocopherols, like gamma- and delta-tocopherol, are almost quantitatively degraded and excreted in the urine as the corresponding CEHCs. All rac alpha-tocopherol compared to RRR-alpha-tocopherol is preferentially degraded to alpha-CEHC. Thus, there must be a specific, molecular role of RRR-alpha-tocopherol that is regulated by a system that sorts, distributes, and degrades the different forms of vitamin E, but has not yet been identified. In this article we try to summarize current knowledge on the function of vitamin E, with emphasis on its antioxidant vs. other properties, the preference of the organism for RRR-alpha-tocopherol, and its metabolism to CEHCs.

http://tocofemax.com.br/site/artigos/1.pdf

Vitamin E: function and metabolism

Tissue-specific functions of individual glutathione peroxidases.

Active spermatogenesis was observed in some of the seminiferous tubules of seleniumdeficient rats born to females on a selenium-deficient diet,and only a very few spermatozoa could be recovered from the cauda epididymis of these animals. The motility of spermatozoa from these males was invariably very poor and the majority of the sperm cells showed breakage near the middle piece or principal piece of the tail. Vitamin E supplementation, even at highly elevated levels (d.a-tocopherol acetate, 1000 ppm) did not alleviate these selenium-deficiency symptoms. Rats receiving selenium-deficient diets with antioxidant supplementation also produced semen, which contained, in most cases, nonmotile spermatozoa. The role of selendiulil on spermatogenesis in rats is apparently specific and cannot be substituted either by vitamin E or by the antioxidants tested in this study.

Effect of Selenium, Vitamin E, and Antioxidants on Testicular Function in Rats

/pdf/specific-effect-of-selenium-deficiency-on-rat-sperm-4w2rqm87th.pdf

Specific Effect of Selenium Deficiency on Rat Sperm

The nutritionally important trace elements share a high biological activity, implemented through association with enzymes, hormones or vitamins. The same activity responsible for physiological responses at extremely low dietary levels implies the potential for metabolic upset when the elements are ingested at elevated, although still relatively low levels. Selenium provides a classic example of this dichotomy of effects and has generated concerns at both ends of its supply spectrum. Experiences in the Dakotas, mid-19th century, led to identification of toxicity symptoms for which selenium was later shown to be responsible, while separate studies showed that excess selenium was teratogenic in the developing avian fetus. These toxic reactions suggested that selenium might be useful in restricting abnormal cell growth, and recent studies have proved it to be anticarcinogenic in certain specific circumstances. Investigation of selenium's nutrient function has been equally interesting, and when Schwarz showed it to be an essential nutrient in 1957, he began an era of intense research activity. Dietary levels of selenium below 0.02 ppm were found to cause deficiency symptoms affecting muscles, liver and pancreas and glutathione peroxidase was shown to be an active form through which selenium acted to prevent such aberrations. Research continues to seek other active organic combinations for selenium to identify interfering compounds that restrict its bioactivity and to explore biochemical mechanisms involved in its toxicity.

The two faces of selenium.

This review addresses the effects of mercury (Hg) in fish as it relates to the health of the fish themselves as well as potential risks of toxicity in wildlife and humans that consume fish. In particular, it addresses selenium (Se) as a bioindicator of susceptibility to harmful effects of Hg exposures and evaluates how Se moderates the toxic effects of Hg in a variety of test animals, emphasizing the importance of these potential effects in fish. A major conclusion of this review is that Hg toxicity risks to animal life cannot be accurately assessed without considering the moderating effects of Se. Therefore, Se:Hg molar ratios and their mathematical inverse are important factors that need to be considered when assessing risks from Hg exposures because exposures are related directly to toxicity outcome. In addition, actual measurement of both beneficial nutrients (e.g., Se, omega-3 fatty acids) and contaminants (e.g., Hg, polychlorinated biphenyls [PCB]) in fish tissue, rather than gross associations betw...

Selenium and Mercury Interactions with Emphasis on Fish Tissue

The effects of selenium and vitamin E on blood selenium levels and tissue glutathione peroxidase activities were determined in sheep fed purified and hay diets. A significant increase of blood levels of this element and tissue glutathione peroxidase activities was found in sheep given selenium as compared to those not receiving this element. Of the tissues examined, the highest glutathione peroxidase activity was found in the heart. Vitamin E had no influence on either the blood selenium levels or upon the tissue glutathione peroxidase activity. With hydrogen peroxide as the substrate, tissue glutathione peroxidase activity was not correlated with the incidence of white muscle disease. Evidence is presented to suggest that 0.1 ppm dietary selenium is not sufficient under some conditions to meet the physiological requirements for this element.

Effects of selenium and vitamin E on blood selenium levels, tissue glutathione peroxidase activities and white muscle disease in sheep fed purified or hay diets.

J. E. Oldfield

Papers

Effect of Selenium, Vitamin E, and Antioxidants on Testicular Function in Rats

Specific Effect of Selenium Deficiency on Rat Sperm

The two faces of selenium.

Selenium and Mercury Interactions with Emphasis on Fish Tissue

Effects of selenium and vitamin E on blood selenium levels, tissue glutathione peroxidase activities and white muscle disease in sheep fed purified or hay diets.