Further insight into the impact of sodium selenite on selenoenzymes: High-dose selenite enhances hepatic thioredoxin reductase 1 activity as a consequence of liver injury

Abstract

Selenium (Se) at supranutritional levels can enhance the activity of glutathione S-transferase (GST), whose gene is a target of nuclear factor erythroid-2 related factor 2 (Nrf2). Recent studies indicated that the thioredoxin reductase 1 (TrxR1) gene could also be targeted by Nrf2. Thus, high-dose Se may stimulate TrxR1 provided it enhances GST activity. Indeed, one study found that Se at supranutritional levels transiently increased hepatic TrxR1 activity. However, another study reported that supranutritional Se had no such effect on hepatic TrxR1 activity. In view of this discrepancy, the present research investigated whether high-dose Se has any impact on hepatic TrxR1. Moreover, we investigated whether Se preferentially activates GST over TrxR1. We observed that when sodium selenite (SS) caused liver injury, both hepatic TrxR1 activity and hepatic GST activity increased. Further experiments indicated that SS increased hepatic GST activity at either toxic or high but non-toxic dose levels; however, increase in hepatic TrxR1 activity occurred only at toxic levels, suggesting that enhanced TrxR1 activity correlates with liver injury. To corroborate this, we showed that hepatotoxic agents, thioacetamide or carbon tetrachloride, caused marked increases in hepatic TrxR1 activity. In conclusion, high-dose SS indeed can enhance hepatic TrxR1 activity, but only on the condition that it causes liver injury. High-dose SS affects hepatic GST more readily than hepatic TrxR1. Thus, the cancer-preventive mechanism of Se at non-toxic supranutritional levels relies more on its modulation of GST rather than TrxR1, at least in liver tissue.

Effects of Acute In vivo Cisplatin and Selenium Treatment on Hematological and Oxidative Stress Parameters in Red Blood Cells of Rats

“…The role of GST is reflected in detoxification, transport, and synthesis, and this is one of the oxidative stress inducible enzymes. Zhang and associates [47] showed that at supranutritional levels, Se could enhance hepatic GST activity. Opposite to these data, our results indicate synergistic inhibitory effects of Se and cisPt on GST activity in RBC.…”

Impact of heat treatment on size, structure, and bioactivity of elemental selenium nanoparticles

“…20 Compared with several extensively studied selenium compounds, ie, sodium selenite, selenomethionine, and methylselenocysteine, selenium nanoparticles show markedly lower acute toxicity and significantly lower short-term and subchronic toxicities, but all these selenium compounds have equivalent efficacy in their ability to increase selenoenzymes. [20][21][22][23][24][25] Furthermore, selenium nanoparticles appear to be more efficient than sodium selenite and selenomethionine in increasing glutathione S-transferase activity, 21,25 and seem to be equally efficient in inducing apoptosis of certain types of cancer cells as methylseleninic acid, a metabolite of methylselenocysteine that is considered to be the most promising selenium compound in cancer prevention. 26 Selenium nanoparticles may enhance selenium permeation and retention in tumor tissues because their blood vessels contain enlarged pore sizes ranging from 100 nm to 800 nm, in stark contrast with the pore sizes of 2 nm to 6 nm in the vessels of healthy tissues.…”

“…28 Selenium nanoparticles have emerged as a novel selenium source with the obvious advantage of reduced risk of selenium toxicity. [20][21][22][23][24][25]29,30 Accordingly, a selenium nanoparticle solution may be added to functional foods, the final products of which may be subjected to heat during processing. An important feature of nanoparticles is their high surface to volume ratio.…”

Biomarkers of Selenium Toxicity after Sub-Acute Exposure in Mice

“…After 2-10 days their levels returned to normal values. Zhang et al [27] exposed mice to Se for 14 days with an i.p. injection of 2 mg selenite/kg bw and found a significant increase in the activities of ALT and AST, a decrease in the liver glutathione peroxidase and SOD, and an increase in GST and Thioredoxin Reductase.…”