Hepato-neuro lab

Oxidative stress

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atome A living organism is constantly subjected to molecular attacks, damaging cells and biological macromolecules.

Reactive oxygen species (ROS)

ROS are molecules derived from oxidation-reduction process. During reduction, a substance gains electrons from a reducing agent who give it them, name as "anti-oxidant". A molecule loses its electron (and a gain of oxygen) is called a "pro-oxidant", as ROS are. They are generally unstable and thus highly reactive.

There are several ROS, these molecules have in common to contain oxygen and are highly reactive. Some free radicals are:

while others are not:

Sources of ROS

The energy fuel of cell is oxygen, a very powerful oxidizing agent. The electrons chain located in mitochondrial membrane is the major ROS production site. Most enzymes involved in ROS generation are:

Electron transport chain

Both complexes of electron transport chain generates ROS

Nitric oxide is produced by nitric oxide synthase (NOS). In addition, phagocytic cells uses ROS as first defense line in innate immunity ("oxidative burst"). ROS are produced by NADPH oxidase family members, and are involved in apoptosis activation, cytokines production, inflammatory and anti-microbial reaction. Finally, ROS may be exogenous, from food or other inputs (smoking, pollution, ...)

Antioxidants

Body defends itself against these ROS, because large quantities are harmful. Many antioxidant molecules are found in mitochondria:

Many enzymatic processes to turn superoxide into single water molecule from superoxide dismutase and catalase. The glutathione system is maintained by glutathione reductase and peroxidase. Also, various redoxines reduce peroxide molecules. Vitamins C and E, polyphenols (red wine), carotenes (fruits and vegetables), flavones (soybeans) are other anti-oxidant molecules, either circulating or cellular.

Oxidative stress

Oxidative stress is defined as a imbalance between anti-oxidant and oxidant molecules. This may come from an increased production of ROS. It may be caused, for example, during an infection or illness, when oxidases are excessively stimulated. Furthermore, it is also possible a declining or dysfunctioning antioxidant defenses.

Effects of ROS

ROS are highly reactive, they can create chemical changes in macromolecules. Cells membranes are prone to peroxidation. DNA and RNA are subject to mutations. Many protein's modifications like nitration or carbonylation could damage proteins causing dysfunction or damage. Some aldheidic products (4-hydroxy-2-nonenal, HNE) get attached to proteins. Too heavy modifications cause cell apoptosis.

In hepatic encephalopathy

It is believed that oxidative stress plays an important role in pathogenesis of hepatic encephalopathy. Studies investigating the role of ammonia in association with oxidative stress are underway (Bosoi et al, 2009).

Ammonia
Animal models