Oxygen free radicals & cellular injury – causes, symptoms & pathology
What are free radicals? Well, in the body, free radicals typically take the form of reactive oxygen species, which include peroxides, superoxide, and the hydroxyl radical.
These chemical species are capable of doing serious damage to tissues because of their molecular reactivity various proteins in the body. This video discusses the pathophysiology of cellular injury due to the generation of reactive oxygen species.
A free radical is a chemical with an unpaired electron. Oxygen is, perhaps, the most well-known free radical. While it’s normally balanced with four pairs of electrons, oxygen is capable of gaining electrons. When an oxygen molecule picks up an extra electron, it becomes a free radical and can cause damage to the body.
Free radicals are created in normal physiologic conditions, as well as abnormal pathologic conditions. Oxidative phosphorylation, a process that aids in making ATP, is an example of a normal physiologic process that creates free radicals. During oxidative phosphorylation, oxygen receives electrons from molecules of C oxidase, and in turn triggers the mitochondria to create a protein gradient that controls the production of ATP.
When oxygen gains one unpaired electron, it becomes superoxide; when it gains two, it becomes hydrogen peroxide. The hydroxyl radical is created when oxygen gains three electrons. When oxygen gains four electrons, it is reduced to water. The gaining of one, two, or three electrons is referred to as a partial reduction of oxygen.
Ionizing radiation is an example of a pathological process that creates free radicals. This occurs when radiation interacts with the water contained in body tissue. The radiation knocks off an electron, creating a hydroxyl radical that can cause damage to cells.
Inflammation is another example of a free radical producing pathological process. Infection triggers a flood of neutrophils that destroy pathogens one of two ways, one of which requires oxygen. An enzyme called NADPH oxidase converts oxygen to superoxide in what’s referred to as an oxidative burst. This stage of the process creates free radicals, while the superoxide is processed into bleach or HOCL.
Contact with metals like copper or iron can also create free radicals. The body creates transference proteins that bind to iron and help control the levels of it in the blood. If iron is not bound, it can create hydroxyl free radicals through a process called the Fenton reaction. A build-up of free radicals due to iron exposure can lead to hemochromatosis and sclerosis in the liver. A build-up of free radicals due to copper exposure can lead to Wilson’s disease.
Free radicals may also be generated by drug exposure. Many drugs, like acetaminophen, are metabolized by the liver. The metabolizing generates free radicals; high doses of these drugs may lead to liver cell death.
One way free radicals cause damage to other cells is through a process called lipid peroxidation. A free radical is in constant search for a balancing electron, and will “steal” one from the lipid of the cell membrane. The robbed lipid is left with an unpaired electron, so it steals one, and the destructive cycle continues.
Free radicals also damage cells by oxidizing the proteins and DNA within them. Oxidation of proteins may affect the cell’s function, while oxidation of DNA can cause cancer.
Antioxidants are the best defense against free radical oxidants. Antioxidants donate electrons to free radicals, eliminating the destructive cycle of lipid peroxidation. Examples of antioxidants include vitamins A, C, and E.
Metal carrier proteins like transference and ceruloplasmin also defend against free radical damage. Transference binds to iron, while ceruloplasmin binds to copper. The proteins then carry the metals to the liver, where it is bound by ferritin and left unable to generate free radicals.
The body also creates enzymes to fight free radicals. Superoxide dismutase takes care of superoxide, catalase takes care of hydrogen peroxide, and glutathione peroxidase takes care of hydroxyl free radicals.
Exposure to environmental toxins may also trigger free radical production. For example, carbon tetrachloride, a chemical used in dry cleaning, is converted by the liver into trichloromethyl radicals. Trichloromethyl radicals damage the proteins, DNA, and cell membranes of the liver. In early stages, the damage is reversible. The first symptom will be swelling of the cells. As damage continues, protein-producing ribosomes are destroyed and protein syntheses decrease. Apolipoproteins also decrease, leaving the liver unable to rid itself of fats.