TOXINS, 
OXIDATIVE STRESS & GLUTATHIONE IN AUTOIMMUNITY

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.

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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.

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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 

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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.