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Toxins in the environment

TOXINS, 
OXIDATIVE STRESS & GLUTATHIONE IN AUTOIMMUNITY

BPA - LEAD - SILICA - MERCURY - CIGARETTE SMOKE - PESTICIDES - MEDICATIONS - CADMIUM - PESTICIDES - AIR POLLUTION - FORMALDEHYDE - PHTHALATES

Various experimental and clinical studies have shown that Autoimmune diseases can be triggered by exposure to a variety of chemicals or drugs.  The mechanisms of toxic dysregulation of the immune system can occur at a cellular and biochemical level:

1) Chemicals can alter cell proliferation, cell apoptosis and T helper cell balance (TH1, TH2, TH17).

2) Chemical haptens and metal ions can interact with human proteins and activate proinflammatory cytokines and trigger T and B cells in particular TH17 which is known for tissue destruction in autoimmune conditions.  

3) Chemicals can affect DNA methylation i.e. epigenetic modification that can cause a change in gene expression. 

4) Chemicals can stimulate the release of Reactive Oxygen Species (see below).

5) Chemicals may compete with thyroid hormones or interfere with iodine transportation that leads to an inflammatory response in the thyroid gland.

6) Chemicals can bind to Immune Cell Receptors triggering inflammatory immune responses. 

7)  Chemicals can deplete Glutathione an important anti-oxidant in the body.

Molecular mechanisms implicated in chemical-induced Autoimmune reactivities.

Reference: (Vojdani, 2014)

doi.org/10.1155/2014/437231

Chemical induced AI

Examples OF TOXINS which can contribute to the 'Chemical Load' of an individual

  • Medication specific immune responses are well researched. Medicines have a great tendency to be cross-reactive with peptide antigens. 

  • Bisphenol A (BPA) is used in the manufacture of  plastic storage containers, water bottles, and food and drink packaging. Evidence highlights the role of BPA in proinflammatory immune responses by enhancing polarisation of immune cells and cytokine production to one that is consistent with proinflammation (see below). 

  • Mercury is a known promoter of autoimmune reactions,  when the amount of mercury in thyroid follicular cells reaches a critical level in people with a genetic predisposition to Autoimmunity, Autoimmune thyroiditis could result.

  • Association between air pollution and Autoimmunity has also been found for multiple sclerosis (MS) – increased concentration of pollutants in the air was correlated with relapses of the disease. 

  • Occupational exposure to silica, pesticides, solvents, and other inhaled substances has been linked to the development of Lupus. 


Lab Testing can measure chemicals in the body through blood chemical antibody tests and urine levels of chemicals.

T cells

BPA (bisphenol A) 

This diagram illustrates how bisphenol A can induce T cell shifts, promoting Autoimmunity. BPA: bisphenol A; IFN: interferon; IL: interleukin; TH: T-helper; T-reg: regulatory T cell.

Reference: (Kharrazian, 2014)

doi.org/10.1155/2014/743616

Oxidative Stress (OS) & Reactive Oxygen Species (ROS)

Oxidative stress is a disturbance in the balance between the production of ROS and antioxidant defences.   

In simple terms, oxidation is the chemical process occurring when a substance loses electrons or gains oxygen.  It is like the process that causes fruit to rot or iron to rust.  If a molecule loses an electron, it becomes unstable. These unstable molecules are often referred to as free radicals.

Free radicals try to steal electrons back from other, more stable cells in order to stabilise themselves.  This causes a cascade of increasing free radical molecules, which in turn causes oxidative stress.  Oxidative stress can cause cell and DNA strand damage, which is why it is thought to be behind  tissue damage, inflammation and a number of health conditions.


Oxidative stress plays an important role in the pathogenesis of a variety of autoimmune diseases and many environmental agents participate in this process.  ROS represent a class of molecules capable of damaging DNA. They are almost always present in the human body since they are produced by cellular metabolism. Superoxide anion radicals (O2−), hydrogen peroxide (H2O2), hydroxyl radicals (OH), and singlet oxygen (O2) are some of the chemical products belonging to the ROS family.

The loss of redox homeostasis generates stressed cells which in turn produce damage-associated molecular patterns (DAMPs) or autoantigens that could initiate innate immunity and adaptive immunity. This series of events leads to the dysfunction and death of cells via an inflammatory cascade. Oxidative stress and Autoimmunity with genetic susceptibility are associated with the pathogenesis of several Autoimmune diseases; however, precisely how these two pathways integrate one with each other is not fully understood 

Neutrophils kill micro-organisms, via phagocytosis.  They release (ROS) and proteolytic enzymes within the phagosome in a process termed the ‘Respiratory Burst’. This process consumes large amounts of oxygen, which is converted into the highly-reactive superoxide radical O2- and H2O2 which together with other chemicals provide a toxic intra-phagosome environment able to kill a broad range of micro-organisms. However, under certain circumstances such as during an Autoimmune response, neutrophils can be triggered to release ROS extracellularly causing damage to host tissues, modification of host proteins, lipids and DNA and dysregulation of oxidative homeostasis

Mechanisms linking environmental agents to the development of Autoimmune Diseases

Oxidative stress-mediated disturbance of Nrf2, induction of NF-kB, PARP1, and NLRP3 can cause activation of both innate and adaptive immune systems, resulting in pro-inflammatory cytokines and production of autoantibodies, leading to tissue damage in Autoimmune disease.  Reactive oxygen species (ROS) and lipid peroxidation-derived reactive aldehydes (HNE and MDA) have the potential to cause protein medications and neoantigen formation, which will activate antigen presentation cells including dendritic cells (DCs) and macrophages (MΦ), that consequently promote activation of T and B cells.


Reference: (Khan MF, Wang H, 2020)

doi.org/10.3389/fimmu.2019.03094

ROS

The link between ROS, oxidative stress and their effects on the human body.

Oxidative stress is the imbalance that occurs when there is an increased production of free radicals that exceeds the body’s ability to neutralize it. Alteration of chemical reactions at the cellular level leads to the appearance of free radicals and peroxides that affect the intracellular structures – proteins, lipids, DNA, with the disruption of intrinsic mechanisms at this level. Free radicals are normally produced in the body due to the influence of external factors, such as pollution, cigarette smoke, or internal, due to intracellular metabolism when antioxidant mechanisms are exceeded.


References: ( Sharifi-Rad M et al., 2020)

doi.org/10.3389/fphys.2020.00694

ROS and their effects

GLUTATHIONE

One of the most essential anti-oxidants for Autoimmunity produced in the body.  It plays a huge role in immune tolerance as well as the following:

  • Is involved in antioxidant processes, has oxidation & reduction capabilities

  • Supports Mitochondria

  • Supports Blood Brain Barrier integrity

  • Supports Lung barrier integrity

  • Supports Regulatory T cells

  • Supports nitric oxide balance

  • Impacts phase 2 liver detoxification pathways

  • Is a natural chelating agent by binding to metals and removing them

Autoimmunity can be affected by the anti-oxidant status of the individual.  The higher the Glutathione levels, the stronger the immune barriers and the ability to clear toxins and free radicals from the body.  Autoimmunity involves inflammation, which increases free radicals.  Toxins also increase free radicals.  Free radicals have unstable electrons, when unstable, they attach to body tissues. Antioxidants bind to free radicals donating an electron to make them more stable and stop tissue destruction.   

Other factors that deplete Glutathione:

Diet - Lack of sulphur and vegetables in diet, pro-inflammatory diet, a diet low in anti-oxidants

Lifestyle - Smoking, Drinking, Overtraining, Medications

Environment - Poor air quality, radiation exposure, Industrial pollutants, Chemical exposures

Health Conditions - Autoimmunity, Inflammatory conditions.


Glutathione levels can be checked with Lab testing and can be supplemented into the diet by Liposomal Glutathione or N-acetyl cysteine.

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