Are you looking at your blood test and seeing high iron levels? Maybe you have a concern about hemochromatosis.We look at the toxic effects of iron.
We need to understand the beneficial or positive effects of iron, as well as the specific damage that occurs in the cells and tissues and where it can target certain tissues more than others. We'll also discuss what you need to know in terms of lab testing and other possible therapeutic interventions when you're having toxic effects of iron.
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Reference link: www.nature.com/articles/s4141...
So, in looking at the toxic effects of iron, we also need to understand what are the benefits of iron? What is it needed for? Most of us know that some forms of iron are needed for making red blood cells and the hemoglobin that transports oxygen to all of our tissues.
Iron is also needed for certain types of white blood cells like macrophages and neutrophils in order for those white blood cells to make things like hydrogen peroxide and the more potent and toxic hydroxyl free radicals. These three radicals are used to kill and get rid of pathogens that are invading our body.
The production of hydroxyl free radicals occurs through the Fenton reaction. You combine hydrogen peroxide and iron, and you get a hydroxyl free radical. This occurs in our white blood cells naturally, but under conditions of high iron levels, it occurs more frequently and even outside of the white blood cells. In normal cellular processes, hydrogen peroxide is generated and is neutralized into water by an enzyme called catalase.
If there are large amounts of hydrogen peroxide around or not enough catalase enzyme present, hydroxyl free radicals will be formed before the catalase enzyme can get to the hydrogen peroxide to turn it into water. The hydroxyl free radical will then react with the cell membrane lipids and turn them into lipid peroxides.
This then creates a chain reaction, causing those lipid peroxides to damage other parts of the cell membrane, and then those causing other parts of the cell membrane to be damaged as well. So, this process of cell membrane lipid damage and subsequent cell death is a process referred to as ferroptosis.
It's implicated in many pathologies affecting different organs, such as the liver, kidney, type 1 diabetes, the pancreas, and different types of cancers as well. So I wanted to drill in on this process a little bit more so you can fully understand just how detrimental toxic iron can be.
We talked about the lipids in the cell membranes getting damaged from the hydroxyl free radical. These fat or lipid-based free radicals are referred to as lipid peroxyl radicals, and they can bump into and also damage polyunsaturated fats (PUFAs) in the cell membrane. And that's sort of that chain reaction that we were talking about. For the initial lipid peroxidation turns into much more lipid peroxidation.
And this chain reaction spreads out, and the lipid peroxyl radicals bump into other polyunsaturated fatty acids, creating new lipid radicals and additional lipid peroxyl radicals.
As this process continues, it amplifies itself until it spreads throughout the whole cell membrane. This has many detrimental effects on the cell membrane and different components of the cell. The peroxidation process also leads to other various reactive compounds, such as malondialdehyde. These byproducts of lipid peroxidation and of this ferroptosis process can further damage proteins, DNA, and cellular signaling, creating all kinds of dysfunction in the cell and eventually cell death.
To summarize, iron can play a crucial role in initiating lipid peroxidation. This happens when there is too much iron around and not enough catalase, which is an enzyme that neutralizes hydrogen peroxide. This can happen when your transferrin binding protein is overly saturated, leading to free iron floating around in your body, tissues, and cells, allowing it to react with hydrogen peroxide.
Once lipid peroxidation occurs, it has detrimental effects on the cell membrane, its integrity, and the signaling that is going on within the cell. This overall global dysfunction in the cell is what we refer to as ferroptosis. Ferroptosis is primarily associated with cellular damage and cell death caused by the accumulation of toxic lipids and lipid peroxidation, as well as iron-dependent oxidative stress.
However, this is not the only reason or mechanism through which iron leads to end-organ damage and dysfunction. Excess iron can accumulate in tissues and cause direct damage as well. This is what we see in hemochromatosis, where there is a combination of direct damage and the ferroptosis process described above, leading to damage to the liver, kidneys, pancreas, testes, joints, and other organs.