Free Radicals in Oxidative Stress, Aging, and Neurodegenerative Disorders

Background

Free radicals are exceptionally reactive atoms or molecules with one or more unpaired electrons and capable of independent existence (Halliwell, 1992). In some instances, free radicals have been used interchangeably with reactive oxygen species (ROS). While this may be correct sometimes, not all ROS are free radicals. Although both generate oxidative stress, ROS are chemically reactive species that contain oxygen and may or may not necessarily be a radical. For example, whereas hydrogen peroxide (H₂O₂) is a reactive oxygen species, it is not a free radical. Other examples include lipid, protein and nucleic acid peroxides. There are also reactive species that are not oxygen species such as reactive species of nitrogen (peroxynitrite (ONOO^•) and nitric oxide (^•NO)), carbon and sulfur.

However, the common denominator in all these terminologies is oxidative stress. Oxidative stress is a chemical process resulting from excessive free radical production due to an insufficiency of the counteracting antioxidant response system (Birben, Sahiner, Sackesen, Erzurum, & Kalayci, 2012). Free radicals and reactive species of oxygen or otherwise participate in chain reactions that culminate in oxidative stress. Normally in aerobic organisms, molecular oxygen is reduced to water via intermediate steps of oxygen reduction that forms O₂^•, H₂O₂and the hydroxyl radical (^•OH) (Halliwell & Gutteridge, 1990). Free radicals and other reactive species’ production in the body is approximately balanced by antioxidant mechanisms needed to mop up these reactive species. However NDs as well as aging, the production of free radical is higher than antioxidant defense. Antioxidants are molecules which at minimal concentrations compared with that of an oxidizable substrate, appreciably slows or stops oxidation of that substrate (Halliwell & Gutteridge, 1990). These enzymatic or non-enzymatic antioxidants, reduce the potential damage of the reactive species thus only minor reactive species induced-damage occurs. Therefore, oxidative stress arises in the event of a significant disparity between the production of free radicals and other ROS and antioxidants production (Halliwell, 2007). In other words, it is a disturbance in the oxidant–antioxidant balance in favor of oxidant mechanisms with a resulting potential tissue damage regarded as oxidative damage (Sies, 1997).