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Natural Product : Se, Selenium

Naturally occurring element. Selenium is incorporated into selenoproteins, such as glutathione peroxidases (GPxs) and thioredoxin reductases (TrxRs), which play critical roles in protecting cells from oxidative damage.
Involved in GPx, TrxR, ans Selenoprotien P which protect normal cells from oxidative stress.
Important in Thyroid hormone metabolism, immune system regulation, reproductive health, and Brain and heart protection.

-recommended daily allowance (RDA) for selenium is about 55 µg/day for adults. (upper tolerance 400ug/day)
-One Brazil nut may contain 50-300ug/nut

Sodium selenite (Na₂SeO₃) is a selenium compound with well-documented anticancer and chemopreventive properties
-Oxidation state: +4 (selenite form of selenium)
-Type: Inorganic selenium compound (water-soluble)

-Sodium selenite generates reactive oxygen species (ROS) selectively in tumor cells.
-Induces cytochrome c release, caspase-3 activation, and DNA fragmentation.
-Reduces VEGF expression and endothelial cell migration.
-Blocks cell division at G2/M phase
-Suppresses MMP-2 and MMP-9 activity
-Activates p53
-Inhibits NF-κB
-PI3K/Akt/mTOR Suppression
-Inactivation of Thioredoxin/Glutathione systems

Narrow therapeutic window:
-Low micromolar (≤5 µM) → anticancer
-High (>10 µM) → toxic to normal cells

Some Selenium Supplements use Sodium Selenite as the active ingredient.
- NOW Foods Selenium, Nature's Bounty Selenium, etc

Other common form is Selenomethionine, as it is better absorbed (found in brazil nuts), but might be less effective?

Sodium selenite might protect against toxicity of AgNPs.

In the chemical synthesis of selenium nanoparticles, a precursor such as sodium selenite (Na₂SeO₃) is dissolved in water to form a homogenous solution. A reducing agent, like ascorbic acid or sodium borohydride (NaBH₄), is then added to the solution. The reducing agent donates electrons to the selenium ions (SeO32−SeO32), reducing them to elemental selenium (Se0Se^0). This reduction process leads to the nucleation of selenium atoms, which subsequently grow into nanoparticles through controlled aggregation.

Se NPs might be hepatoprotective.

Selenium nanoparticles (SeNPs) are a biocompatible, less-toxic, 
and more controllable form of selenium compared to inorganic salts (like sodium selenite).
Major SeNPs hepatoprotective mechanisms
Mechanism	              Description	                       Key markers affected
1. Antioxidant activity	      SeNPs boost antioxidant enzyme          ↓ ROS, ↓ MDA, ↑ GSH, ↑ GPx
                              systems (GPx, SOD, CAT) and scavenge 
                              ROS directly.	
2. Anti-inflammatory effect   Downregulate NF-κB, TNF-α,              ↓ TNF-α, ↓ IL-1β, ↓ IL-6
                              IL-6, and COX-2 pathways.	
3. Anti-apoptotic action      Balance between Bcl-2/Bax and reduce    ↑ Bcl-2, ↓ Bax, ↓ Caspase-3
                              caspase-3 activation in hepatocytes.	
4. Metal/toxin chelation      SeNPs can bind or transform toxic       ↓ liver metal accumulation
                              metals (Cd²⁺, Hg²⁺, As³⁺) 
                              into less harmful complexes.	
5. Mitochondrial protection   Maintain membrane potential,            Preserved ΔΨm, ↑ ATP
                              prevent mitochondrial ROS burst, 
                              and ATP loss.	
6. Regeneration support	      Stimulate hepatocyte proliferation      ↑ PCNA, improved histology
                              and repair via redox signaling 
                              and selenoproteins.

Comparison: SeNPs vs. Sodium Selenite
Property	             SeNPs	                   Sodium Selenite
Toxicity	             Low	                   Moderate–high
Bioavailability	             Controlled, often slow-       Rapid, less controllable
                             release	
ROS balance	             Adaptive, mild antioxidant	   Can flip to pro-oxidant easily
Safety margin	             Wide	                   Narrow
Hepatoprotection	     Strong, sustained	           Protective at low dose, 
                                                           toxic at high dose


"30 mg of Na2SeO3.5H2O was added to 90 mL of Milli-Q water. Ascorbic acid (10 mL, 56.7 mM) was added dropwise to sodium selenite solution with vigorous stirring. 10 µL of polysorbate were added after each 2 ml of ascorbic acid. Selenium nanoparticles were formed after the addition of ascorbic acid. This can be visualized by a color change of the reactant solution from clear white to clear red. All solutions were made in a sterile environment by using a sterile cabinet and double distilled water."




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