Oxidative Stress and Disease

Your Guide to a Healthy Life that Will Make You Better Prepared for Life's Challenges.

What is oxidative stress and why it needs to be under control

More than 95 % of the oxygen consumption in body tissues for energy production and other biochemical reactions involves the enzymatic reduction of oxygen to water or hydroxyl compounds without the production of any reactive species or free radicals such as superoxide(O2--) and hydroxyl radical(HO.) as they are commonly known. On the other hand, hydrogen peroxide is not a free radical and its oxidation reactions with organic substrates proceed rather slowly. However, in the presence of metal ions such as iron it gets into redox reactions with the generation of hydroxyl radical, which can create a lot of damage to macromolecules and cellular structures. The first two are oxygen-centered free radicals because they possess one unpaired electron, which makes extremely reactive and thus short-lived.

By losing or gaining one electron a molecule becomes a free radical. In general, any molecule with an unpaired electron is a free radical. Most of the free radicals in the human body are oxygen-derived ROS). The effect exerted by free radicals in the body is called oxidative stress. Apart from oxygen there are lots of other molecules that can turn into free radicals such as those found in car exhaust, cigarette smoke, industrial emissions, etc. In so doing, they start attacking other molecules snatching electrons from them in order to return to the ground state which is energetically stable. This continuous process is called a chain reaction. The role of antioxidants is to stop the propagation of the chain reaction, in other words to terminate it. DNA, unsaturated fatty acids and proteins are the usual targets of free radicals in the cell. Survival depends on how well an organism is equipped to stand the free radical attack.

The oxidative stress is characterized by a continuous production of free radicals spanning the cellular -> tissular -> whole body range. This process may proceed faster or slower depending on several factors:

  • the overall production of free radicals
  • the efficiency of the antioxidant systems
  • the level of antioxidants supplied through the daily diet

Free radicals are generated during normal cell metabolism, the immune system activity such as fagocytosis of pathogenic bacteria but also by UV and X-ray radiation, environmental pollutants and as a result of metabolization of certain drugs. The ROS generated by the processes shown on the lefthand side can cause a multitude of effects within cells, such as gene mutation, alteration of cellular membranes function due to the oxidation of lipids in the membrane and enzyme inactivation among other things. These combined actions lead to changes in cell metabolism and ultimately to conditions, such as cardiovascular disease, cancer, autoimmune disorders, premature aging, to mention just a few. Some of these conditions usually take years to manifest so people do not notice that there is something wrong going on.

Living cells are extremely complex structures. In many ways the main cell compartments can be likened to some of the organizations that make a city work. In the table below you can see what cell structure would be equivalent to what city organization. Well, ROS can hit almost all cellular organelles though some get more hit than others.

Nucleus City Hall
Endoplasmic reticulum Manufacturing plants
Mitochondria Power plant      High O2- activity
Golgi apparatus Packaging & distribution center
Lysosomes Recycling plant
Microfibrils Infrastructure(highways, roads,
power lines, water mains, etc.)
Cell membrane City boundaries - with its gateways, e.g. railways stations, airports
Cell cytoplasm Residential areas, city public parks, squares, etc.       Moderate O2- activity

Research has consistently shown that all cell structures are subject to free radicals attack by virtue of the fact that they are surrounded by a double layer lipid membrane containing variable amounts of unsaturated fatty acids, which are easily oxidized by ROS. Changes in their chemical and physical properties lead to changes in their biological function and when these changes become irreversible a clinical condition becomes apparent. When tissues are subjected to oxidative stress such as, exposure to irradiation, cigarette smoke or other pollutants the ROS generated in the process can attack several intracellular targets:

  • the DNA in the nucleus by site-specific HO. attack resulting in DNA fragmentation. If the damage to the DNA molecule is not promptly repaired (by several repair enzymes), mutation can result. Mutations in the DNA strands have been long known to be associated with the development of cancer and other degenerative illnesses.
  • the unsaturated fatty acids in the cell membranes(these include the membrane surrounding the cell as well as other intracellular organelles, in a process called lipid peroxidation.
  • proteins and enzymes present in the cytosol (the cell compartment that contains molecules not bound to any subcellular fraction). By reacting with ROS the enzymes are inactivated.

There is a great deal of evidence that free radicals are involved in many human diseases. However, the free radicals are a complicating factor of the pathological condition and not necessarily the primary cause. Their involvement depends on the nature of the disease process. For instance, the increased lipid peroxidation observed after impact injury to the brain appears to contribute to post-injury tissue breakdown. The increased lipid peroxidation seen in the muscles of patients with muscular dystrophy may be a consequence of tissue damage and not a factor responsible for it. That is why in this latter case, antioxidant supplementation may not be of any great help. Several medical conditions in which free radicals, particularly those of oxygen may play a role are:

Accelerated aging
Acute pancreatitis
Arthritis and other autoimmune diseases
Diabetes, diabetic cataract
Drug toxicity
Neuronal stress (related to cognitive function)
Inflammatory bowel disease
Liver cirrhosis
Macular degeneration of the retina
Nutrient deficiency
Parkinson's disease and possibly the Alzheimer's disease
Premature retinopathy
Reduced immune system function
Rheumatoid arthritis

In the face of this free radical onslaught against body tissues what can we do? Well, we get the army of antioxidants to protect us against the deleterious action of ROS and other reactive molecules. As mentioned before, fresh fruit and vegetables contain a host of antioxidant factors that can keep free radical activity in check. For those working in toxic or stressful environments additional antioxidant defence can be obtained from nutritional supplements.

By ensuring an adequate daily intake of antioxidants, either from diet or nutritional supplements we can expect:

  • Increased resistance to infections.
  • Increased energy for both physical nd mental activities.
  • Increased protection against free radicals-induced mutations in the DNA molecule, that can lead to degenerative diseases, such as cancer.
  • Slowing down the aging process.
  • Increased chances for a longer life span and a decreased chance to develop old age-related illnesses.

Bottom line is that the body should not be left without an adequate supply of antioxidants. By doing this and other things related to diet and a healthy lifestyle we are in a better position to prevent degenerative diseases and slow down the aging process. To further illustrate this point you may want to see this PowerPoint presentation. (You must have Microsoft PowerPoint installed on your computer to view this presentation as well as Internet Explorer 6.0 or later. Please wait for 1-2 min. for the video clips to load since they are larger files. High speed internet connection is also required.)

Additional info:
1. on the role of cholesterol and lipids in the development of atherosclerosis: this presentation on YouTube.
2. on the role of free radicals in aging and the benficial effect of L-acetyl carnitine: lecture by B. Ames on Google Videos.