4. Free radicals

Free radicals are atoms, ions or molecules  which have, on the external orbital, unpaired electrons , which confers them a high chemical reactivity and the increased tendency to attack other molecules in order to “steal” their electron, necessary for stabilization. Generating in their turn reactive species which will capture other electrons with the same purpose, the radicals take part in chain reactions, of radical addition and substitution. Their negative influence translates in the fact that they destabilize the cells by the attack on the molecules that form the cells (the lipids and proteins in the cell membrane, mitochondrial DNA etc.), producing mutations or even cellular death.

Some radicals have high reactivity and instability, being the most dangerous for the human organism.

Free radicals stock oxygen and facilitate burning. (This piece of information is mentioned in the book “Forbidden Health” by Andreas Kalcker). As such, the burning of Oxygen releases heat (hot flushes). This is the explanation for my hot flushes (oxidative stress) that I’ve been experiencing since the beginning of my agony.

For the most part, heavy metals bind to oxygen, nitrogen and to the thiol (sulfhydryl) groups in the proteins, leading to the alteration of enzymatic activity. This affinity of metals for sulfhydryl groups is also protective in the homeostasis of metals. The high synthesis of proteins which bind heavy metals as a response to the high level of metals in the body is the first defense mechanism against poisoning. For instance, metalloproteins are induced by many metals. These molecules are rich in thiol ligands which can allow the high affinity binding of Cadmium, Copper, Silver and Zinc among other elements. Other proteins involved in the transport of heavy metals and their excretion by ligands formation are: Ferritin, Transferrin, Albumin and Hemoglobin.

The organs of which functions are the most affected are: the brain, the peripheral nerves, the hematogenous marrow, the gastroduodenal tract, the cardiovascular system and the renal system. To a lesser extent, the toxicity of Lead affects the musculoskeletal system and the reproductive system. The affected organs and the severity of symptoms depend on: the quantity of metals in the body, the kind of metal, the patient’s age, the chronicity and extension of exposure.

Free radicals are substances which derive from incompletely oxidized compounds, which underwent partial oxidations, having in their structure oxygen groups capable of initiating at the surface of cellular membranes or even inside of the cells, aggressive reactions of oxidation. Free radicals come from the processes that happen in the organism (phagocytosis, incomplete

catabolism, energy production, hepatic detoxification) and from the external environment (heavy metals, cigarette smoke, polluted air, certain foods and medicine, fountain or tap water…

Endogenous sources  of free radicals (from the inside of the human body):

1.The intra-cellular compartments:

*mitochondria

*the endoplasmic reticulum

*peroxisomes

*nuclei

*the cytosol

*plasma membranes

2.The extra-cellular spaces (even they can generate ROS – reactive oxygen species)

3.Endogenous transition metals which transport electric charges – Iron, Copper, Manganese – and which take part in Fenton reactions which generate Hydroxyl Radical (which has extremely harmful effects).

The major site in ROS (Reactive Oxygen Species) production in most mammalian cells  is the mitochondrial electron transport chain.

Other compounds (radical and non-radical) are the Reactive Nitrogen Species (RNS) which cause nitrosative stress. These free radicals are also very unstable.

Reactive Nitrogen Species (RNS) are very often linked to Reactive Oxigen Species (ROS). ROS cause oxidative stress and RNS produce nitrosative stress, which can lead to serious health problems (diabetes, Alzheimer, cancer etc).

The enzymes which catalyze the chemical reactions that generate ROS are:

*peroxidases

*NADPH oxidase

*NADPH oxidase isoforms (NOX)

*xanthine oxidase (XO)

*lipoxygenases (LOXs)

*glucose oxidase

*myeloperoxidase (MPO)

*nitric oxide synthase

*cyclooxygenases (COXs)

A part of the Reactive Oxygen Species (ROS) are produced in the gastro-intestinal tract (GI).

Exogenous sources of free radicals (from the environment):

1.exogenous heavy metals (silver, mercury, cadmium, aluminium, lead

2.radiation (UV radiation, ionizing/non-ionizing radiation, electro-magnetic radiation

3.polluting agents, pesticides

4.ultrasounds

5.microwaves

6.metabolism of some medicine (especially antitumoral medications), drugs…

Experimental data shows that in a single inhalation, in the body enters a volume of oxygen that can generate a billion free radicals which, in their turn, by chain reactions that happen almost instantly, will alter other molecules by  the detachment (snatching) of electrons and damaging them.

In small quantities, free radicals have an important role in the fight against bacteria, viruses, chemical pollutants and toxins.

Harmful effects appear when the quantity of reactive species surpasses the organism’s defence capability, their positive action being basically canceled.

Oxidative stress and the organism’s degradation

The most reactive species of Oxygen – the radicals Hydroxyl, Superoxide and Peroxide – play an important role in the process of premature aging, manifested by the loss of resilience and elasticity of the tissues, decrease of enzymatic activity, as well as in the appearance of diverse forms of cancer (because of the reactions with cellular DNA and the activation of oncogenes), in coronary atherosclerosis (by the attack on the fats and HDL-cholesterol), in pulmonary emphysema (the radicals in the cigarette smoke are involved in the deactivation of enzyme alpha-1-antitrypsin in the lungs), arthritis, deafness, Alzheimer, Parkinson, pulmonary fibroses etc.

Oxidative stress means an exaggerated production of free radicals and reactive species  (an imbalance between oxidants and antioxidants).  

Oxidative stress is the term used for the ailments caused by the Reactive Oxygen Species named Free Radicals. Oxidative Stress is defined as the imbalance between oxidants and antioxidants, in favour of the oxidants, with destructive and pathogenetic potential. Depending on its intensity, oxidative stress can manifest intra-cellularly or extra-cellularly. Intra-cellular oxidative stress can determine cellular necrosis or the less or more pronounced disorganization of the cell, with catastrophic effects for a cell that is incapable to reproduce itself. Extra-cellular oxidative stress is also cytotoxic.

Oxidative stress has very grave effects on the brain, organ characterized by an intense activity, therefore by quite a serious degradation. Cerebral ageing involves the decrease of the number of neurons and the increase of the number of glial cells (reactive gliosis), the most affected elements being he synapses.

The regions of the brain do not degrade equally: certain regions may lose up to 60% of the neurons as life goes by, while others are almost entirely spared from neural loss.

The brain has an efficient weapon to fight against oxidative degradation which is neurogenesis (the forming of new neurons). This process has been identified so far in two regions of the brain: the Subventricular Zone (SVZ, of the lateral ventricles) and the Subgranular Zone (SGZ, in the dentate gyrus of the hippocampus).

Means of  antioxidant defense:

Fortunately, the human organism possesses an enzymatic equipment and a genetic control which allow it, to a certain extent, to fight radical species. Antioxidants can be enzymatic and non-enzymatic:

*Superoxide Dismutase (SOD)

*Catalase (CAT)

*Glutathione peroxidase (GPx)

*Glutathione reductase (GR, GSR)

*Heme oxygenase (HO)

*Glutathione

*Thioredoxin (Trx)

*Thioredoxin reductases (TrxR)

*Melatonin

*Polyphenolic antioxidants

*Ceruloplasmin

*Lycopene (important for the prevention of prostate cancer, according to recent studies)

*Vitaminele A, C, E

*Selenium

*Melanin (“substantia nigra”, black pigment, is a stable free radical, a biological polymer, a pigment whose deterioration can cause Parkinson or deafness. It determines the colour of the skin. It protects against thermal stress, heavy metals, free radicals, reactive species, UV radiation. It has antioxidant properties.

Antioxidants act by donating an electron to a free radical, which will become a non-reactive species, concluding the chain of radical reactions. Yet, the action of antioxidants also has a downside: the giving of an electron has as a direct consequence the transformation of the antioxidant into a radical in its turn, so that, depending on the reaction conditions, a substance can be an efficient antioxidant or, the opposite, a prooxidant (an example is uric acid, antioxidant which, in certain conditions, participates in reactions with peroxide, importantb process in the ethiology of gout).

The organism also makes use of a second weapon against free radicals: apoptosis (known as programmed cellular death), by which the cells deactivate their enzymes and disassemble their cellular components in situations of heavy degradation. This degradation is caused, among other things, by oxidative stress.

A genetically coordinated and controlled process (which initially was thought to be a chaotic physiological process), apoptosis is completed by the ingestion of apoptotic cells by the macrophages, which takes place without the leaking of the cellular content or of the reactive radical species  to the extracellular space, without inflammatory response or damage to the surrounding cells.

Programmed cell death is an efficient method of slowing down or halting of the development of malignant tissues and, subsequently, of cancer.

In spite of these defence mechanisms, the fight against free radicals is an unequal one, to the detriment of the human organism, whose degradation is more and more accentuated nowadays.

This aspect hasn’t been ignored by researches who proposed countless formulations with antioxidant properties. The most efficient are antioxidant supplements which act synergistically: vitamins A, C, E, Selenium, Coenzyme Q10, Zinc and many others… Ageing is a biochemical process, therefore partially controllable, and not a strictly chronological one.

Free radicals and their oxidation potential (measured in volts):

MoleculeOxidation potential (volts)
Hydroxyl radical (OH)2.80
Molecular chlorine1.36
Hypochlorous acid (“free chlorine”)1.49
Ozone2.07
Hydrogen peroxide1.78
Chlorite ion1.57
Chlorine dioxide0.95

Link:       

Chlorine Dioxide Properties

https://www.carbotecnia.info/aprendizaje/quimica-del-agua/dioxido-de-cloro-y-efectos-en-la-salud/

Hydroxyl Radical – together with Singlet Oxygen (1O2) , Hydroxyl Radical (HO) is the most powerful species of Oxygen (O2).  Hydroxyl Radical reacts with great speed with absolutely any organic molecule: glucides, aminoacids, lipids, nucleic acids (DNA, RNA), organic acids.

Link:      

Stresul oxidativ     

https://www.qdidactic.com/didactica-scoala/biologie/stresul-oxidativ131.php

Hydroxyl Radical is the most reactive radical known in chemistry. It can interact with the nitrogenous bases of nucleic acids (DNA and RNA) and alter the genetic information of cells or stimulate the peroxidation of lipids in which it attacks polyunsaturated fatty acids, transforming them into oxidants. Just one Hydroxyl Radical can transform hundreds of molecules of fatty acids into hydroperoxides which when they decompose, produce aldehydes, real poisons for the cellular membranes.

Link:       

Influence of free radicals on cell aging    

https://www.elsevier.es/es-revista-offarm-4-articulo-influencia-los-radicales-libres-el-13034834#:~:text=H%2D.-,El%20.,lip%C3%ADdica%2C%20en%20la%20que%20el%20.

Hydroxyl Radical – the radical that caused me dozens of agonizing moments

Although I don’t have any formal training in chemistry, I concluded many times that the agonizing sufferings that I had (and still have, especially at night) through my heart, chest, belly, brain, arms etc could be triggered by an extremely reactive free radical like Hydroxyl Radical. The agonizing moments with hot flushes/oxidative stress (due to the burning of Oxygen), agonizing sufferings, tachycardia, the disappearance of sleep and yawning, violent spasms (electric discharges in my brain) followed by waking up etc appear, in my opinion, when this radical (and others similar) “pluck” electrons that they need for stabilization from different locations in my body. This results in sufferings impossible to describe in words, sometimes I’m so sick I fell like I’m dying.

Sometimes I start agonizing during the night after I inhale air, this clearly indicates a presence of

Reactive Oxygen Species (ROS) in my tissues.Redox reactions (reduction – oxidation)

Oxidants (oxidizing agents)

Oxidants are substances that have the ability to oxidize other substances (to make them lose electrons). The oxidant takes electrons from another substance and is thus itself reduced. Oxygen is an oxidant (oxidizing agent). Because it “accepts” electrons, the oxidizing agent is also called an electron acceptor.

Reducers (reducing agents, reductants)

Reducing agents (or reductants, reducers) are substances that have the ability to reduce other substances (cause them to gain electrons). The reductant transfers electrons to another substance and is thus itself oxidized. Because it donates electrons, the reducing agent is also called an electron donor.

Oxidation means loss of electrons (oxidation state increases). Reduction means gain of electrons (oxidation state reduces).

As I have already mentioned, the highly reactive free radicals in my body exist because in my tissues are still being liberated ions of silver, mercury, gadolinium etc…

Links/sources:

Free radicals and cellular aging

https://www.revistagalenus.ro/arhiva/revista-galenus-2010/radicalii-liberi-si-imbatranirea-celulara/

Properties of chlorine dioxide

https://www.carbotecnia.info/aprendizaje/quimica-del-agua/dioxido-de-cloro-y-efectos-en-la-salud/

Oxidative stress

https://www.qdidactic.com/didactica-scoala/biologie/stresul-oxidativ131.php

Influence of free radicals on cellular aging

https://www.elsevier.es/es-revista-offarm-4-articulo-influencia-los-radicales-libres-el-13034834#:~:text=H%2D.-,El%20.,lip%C3%ADdica%2C%20en%20la%20que%20el%20.

Hydroxyl radical

https://pubchem.ncbi.nlm.nih.gov/compound/157350l

Hydroxyl radical

https://en.wikipedia.org/wiki/Hydroxyl_radical

What is Fenton’s Reaction?

https://byjus.com/chemistry/fentons-reaction/

What are Free Radicals?

https://byjus.com/chemistry/free-radicals/

Free Radicals: Properties, Sources, Targets, and Their Implication in Various Diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310837/

NADPH—The Forgotten Reducing Equivalent

https://cshperspectives.cshlp.org/content/13/6/a040550.full#sec-5

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4044300/

L-Alliin, Hydroxyl radical scavenger (ab141896)

https://www.abcam.com/products/biochemicals/l-alliin-hydroxyl-radical-scavenger-ab141896.html

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106107/

Bioproduction, characterization, anticancer and antioxidant activities of extracellular melanin pigment

https://www.nature.com/articles/srep42129

Oxygen

https://en.wikipedia.org/wiki/Oxygen

Oxidizing agent

https://en.wikipedia.org/wiki/Oxidizing_agent

Redox

https://en.wikipedia.org/wiki/Redox

[Book] Forbidden Health (Andreas Ludwig Kalcker, 2016)

The intoxicațion with heavy metals  (romedic.ro)

https://www.romedic.ro/intoxicatia-cu-metale-grele

Oxidative stress  (Bioclinica)

https://bioclinica.ro/pentru-pacienti/informatii-analize/stres-oxidativ