Tuesday, May 27, 1997
A recent report by a University of California at Davis environmental toxicologist suggested that the volatile chemicals in the aroma from freshly brewed coffee could have antioxidant properties.
This may have piqued public interest in the benefits of antioxidants; however, biotech companies are seeking more specific and physiological means of protecting against oxidative stress and free radical damage that increasingly is seen as a challenging complication in many different diseases.
And while several pharmaceutical companies have fallen short in their attempts to alleviate problems associated with oxidative stress, younger biotech companies are developing new approaches to the problem.
Oxidative stress refers to the damage done to cells and tissues by oxygen-containing free radicals and other reactive oxygen species (ROS) such as superoxide radicals, hydroxyl radicals, and hydrogen peroxide.
Free radicals are molecules with an odd number of electrons, and thus an unpaired electron, which makes them highly reactive in an effort to find a free electron on another molecule with which to pair.
Specifically, oxygen radicals can oxidize proteins, altering or destroying their function, or oxidize lipids, causing a chain reaction leading to loss of cell membrane integrity. Hydrogen peroxide, which breaks down to produce hydroxyl radicals, can also activate NF-kB, a transcription factor involved in stimulating inflammatory responses.
Living cells constantly produce oxygen free radicals and hydrogen peroxide as a by-product of metabolism and energy production by mitochondria. Cells have defense mechanisms against this internal bombardment, but in certain cases free radicals can be overproduced, or the natural defenses weakened, leading to oxidative stress.
Normally, the inside of a cell is a reducing environment, which helps to prevent oxidative damage. For example, in a reducing environment disulfide bonds (S-S) do not spontaneously form because free sulfhydryl groups are kept in the reduced state (SH), preventing protein misfolding and aggregation. This environment is maintained by natural antioxidant molecules, such as glutathione and vitamin E, and enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase.
In cases of injury or disease, these natural defenses can be overwhelmed by sudden increases in ROS production. During inflammatory responses, for example, phagocytes release huge amounts of ROS in an "oxidative burst" intended to kill invading bacteria. This normally protective mechanism can cause unwanted tissue damage in cases of acute inflammation. Since levels of the protective SOD enzyme naturally decline with age, oxidative stress also may contribute to the aging process.
Therapeutic approaches to oxidative stress have focused on these natural defense mechanisms. Historically, SOD itself was used in several clinical trials. However, that straightforward approach suffered from several drawbacks. Newer therapeutics attempt to replenish glutathione levels, mimic the activities of glutathione peroxidase, SOD, or catalase, or improve upon the activity of vitamin E.
Oxidative stress, rather than being the primary cause of any one disease, is a secondary complication in many. The accumulation of oxidative stress is thought to be a contributing factor to tissue damage in conditions ranging from autoimmunity, inflammation and ischemia, to head trauma and neurological disorders such as stroke, Parkinson's and Alzheimer's.