PARTNER FEATURE ▶▶▶
Figure 2 – The effect of oxidizing conditions on the recovery of synthetic L-SeMet and peptide bound SeMet (Selenium yeast).
100 80 60 40 20 0
0
Synthetic L-SeMet 0.125
0.025 0.05 0.125 0.25
Selenium yeast SeMet H202: SeMet molar ratio
forms of the same synthetic selenium source are also of interest. Clearly, when considering selenium sources, one cannot class them as all being equal.
The reasons behind the toxicity differences In terms of understanding the toxicity differences among selenium sources, it can be useful to examine the biochem- istry behind selenium and its potential to act negatively at a cellular level. The pro-oxidant properties of selenium sources, such as so- dium selenite, originate from their conversion into selenide or selenols, which are readily oxidised and generate reactive oxygen species (ROS). The toxicity of selenite is well docu- mented as being mainly caused by DNA damage due to the induction of ROS-dependent DNA strand breaks and/or base oxidation, leading to apoptotic and necrotic cell death. More recent research has shown that freely accessible selen- ocompounds (such as chemically synthesised selenium) can have pro-oxidant properties, which are initiated in the same manner as sodium selenite but can be further enhanced due to the initiation of additional cycles of oxidation/reduction. Ultimately these redox cycles consume intracellular antioxi- dants such as GSH and, consequently, the reducing cofactor NADPH. Not only can such selenocompound-induced redox cycling lead to antioxidant imbalance; it can also lead to in- creased and sustained production of ROS, which can further damage nucleic acids, proteins and lipids. In addition, oxidised selenols will catalyse the formation of disulfide bridges between low molecular-weight thiols and proteins, potentially leading to protein inactivation or aggre- gation. Newer studies indicate that the toxicity of freely accessible selenocompounds results from their conversion into sele- nocysteine, a selenoamino acid with the ability to mediate proteotoxic stress, thus playing a role in selenium toxicity that was underestimated until now. The inherent risk of toxicity from selenocysteine mediated
24 ▶ ALL ABOUT FEED | Volume 30, No. 5, 2022 0.5 0.75 1
proteotoxicity requires further research to fully understand the implications associated with its cellular generation. It may well be that the enhanced toxicities of the chemically synthesised analogues are due to increased redox cycling and/or increased induction of proteotoxicity due to enhanced selenocysteine synthesis at a cellular level, leading to acute oral toxicities of similar impact to that of inorganic sodium selenite.
Selenium yeast has enhanced stability A benefit that organic selenium yeast provides in this regard is the stabilising influence that peptide and protein incorpo- ration of selenium provides. By incorporating selenium into peptides and proteins rather than amino acids, the potential for instability is vastly reduced. Significantly, the impact on ROS-mediated DNA, protein and lipid damage at a cellular level is negated. In contrast, chem- ically synthesised sources do not have the protecting benefit of yeast protein incorporation and have been shown to have negative cellular impacts. The instability of synthetic selenoamino acids is well docu- mented. Older studies, for instance, highlighting this phe- nomenon, subjected samples of synthetic L-selenomethio- nine and organic selenium yeast to oxidising conditions in the form of a peroxide challenge. These results are illustrated in Figure 2, whereby, upon increasing the oxidising conditions of the solution, the recovery of synthetic L-selenomethionine in its pure form rapidly declines. In contrast, recovery of selenomethionine from the organic selenium yeast remained constant under the same conditions, thus illustrating its greater stability and reduced susceptibility to oxidation. While not a direct in vivo measurement, this simple technique can usefully indicate the potential stability or instability of trace element forms in an oxidising environment.
Anti-oxidant vs. pro-oxidant The main purpose of adding selenium to a diet is to protect against oxidative stress. The primary result of oxidative, or oxygen radical-induced, stress is DNA damage. Research which assessed the differential effects of sodium selenite, synthetic L-selenomethionine and selenium yeast on gene expression in an animal model, produced some notable find- ings. The authors examined the induction of genes and pro- teins linked to DNA damage in addition to physical markers of oxidative stress (Figure 3). They found that expression of the DNA damage response gene Gadd45b was consistently lowered its expression in all tissues following organic sele- nium yeast supplementation (Figure 3A). Inorganic sodium selenite reduced Gadd45b expression in the cortex and gas- trocnemius and the synthetic selenium source was limited in providing cellular benefits and only reduced its expression in the cortex (Figure 3A).
% Recovery
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36
