Free Radical Injury - An Overview

What Are Free Radicals?

Free radicals are defined as molecular species containing unpaired electrons in the atomic orbital capable of independent existence. Atoms are surrounded by electrons that orbit around the atomic nucleus in a specific path called orbit or shell. Each shell is full of electrons, and once the shell is complete, electrons begin to occupy the next shell. If the atom's outer shell is incomplete, it starts bonding with another atom using its electrons. These atoms are known as free radicals. Free radicals are reactive, unlike atoms with their shell complete with electrons. These free radicals are unstable and can donate and accept electrons from other molecules. Superoxide anion radical, hydrogen peroxide hypochlorite, free oxygen, hydroxyl radical, and nitric oxide radical are the free radicals seen in many diseases. These reactive species degrade the nucleus and cell membranes to gain stability. Biologically vital molecules like nucleic acids, proteins, lipids, and carbohydrates are damaged during the reaction. Free radicals induce autocatalytic reaction (a reaction where the product acts as a catalyst for the subsequent response) and thus disturb homeostasis and cause cell damage.

How Are Free Radicals Produced in the Body?

Free radicals and other reactive oxygen and nitrogen species (RONS) are produced either during body metabolism or due to exposure to X-rays, chemicals, carcinogenic substances, ozone, and air pollutants. The free radical formation is a continuous process caused by enzymatic and non-enzymatic reactions in the body. Enzymatic reactions like phagocytosis and respiratory chain in the mitochondria and prostaglandin synthesis generate free radicals.

Internal Sources of Free Radicals Are:

• Inflammation.

• Phagocytosis.

• Prostaglandin synthesis.

• Respiratory chain.

• Exercise.

• Peroxisome.

• Ischemia.

• Mitochondrial reaction.

External Sources of Free Radical Production Are:

• Cigarette smoking.

• Air pollutants.

• Chemical solvents.

• Alcohol.

Although the body produces free radicals naturally, lifestyle factors like exposure to carcinogenic substances enhance their production. This theory explains the reason for cancers and cardiovascular diseases.

What Is the Mechanism of Free Radical Injury?

• Damage to the Proteins- Products formed due to oxidative stress (reaction when a substance comes in contact with oxygen or any oxidizing substance) damage the enzymes and receptors' activities. These proteins contain reactive groups that damage cell function and membrane, thus altering signal transduction mechanism, enzymatic activity, heat stability, and proteolytic activity that leads to aging. Protein damage occurs in three ways:

  • Peptide Fragmentation - Breaking of protein.

  • Protein Cross-Linkage - Protein-protein cross-linking is due to a reaction with lipid peroxidation products.

  • Oxidative Modification of Amino Acids - Amino acids like methionine, arginine, cysteine, and histidine are most prone to oxidation reactions.

• Damage to DNA - DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are prone to oxidative damage. For example, oxidative damage of mitochondrial DNA is considered one reason for aging and cancer. Purines are oxidatively modified to 8-hydroxy 2-deoxyguanosine, a biological marker for oxidative stress.

• Damage to Lipids - Oxidative degradation of lipids is caused by lipid peroxidation. Lipid peroxidation is a process in which free radicals attack lipids that contain carbon-carbon, double mainly polyunsaturated fatty acid (PUFA). By-products of lipid peroxidation, like alkanes and isoprostanes, have been identified as biomarkers in diabetes, neurodegenerative disease, and ischemic injury.

What Are the Biological Effects of Free Radical Injury?

Genetic and environmental changes modulate free radical reactions, which form the basis for age-related diseases. Cancer and atherosclerosis have been established as free radical diseases. Free radical reactions caused due to ionizing radiation can cause tumor formation. Researchers have also found a relationship between fats and oils consumption and the associated death rates (mainly atherosclerosis) due to lipid peroxidation. The free radicals induce endothelial cell injury and cause changes in the arterial walls.

What Is Oxidative Stress?

Oxidative stress occurs due to an imbalance between the free radicals and antioxidants produced in the body. It causes damage to lipids, proteins, nucleic acids, and also to various molecular species. Short-term oxidative stress occurs in injured tissues due to excessive exercise. The wounded tissue produces free radical-generating enzymes like lipoxygenase, and xanthine oxidase, activation of phagocytes, and disruption of the electron transport system. Cancer initiation, promotion, and progression have also been attributed to the imbalance between free radicals and antioxidants.

What Is the Importance of Free Radicals?

Free radicals are vital for several biological processes like phagocytosis (intracellular destruction of bacteria by phagocytes), maintaining homeostasis, and cell signaling. In addition, free radicals cause aging, a typical phenomenon occurring in all living beings. Free radicals bring adverse changes in the body, which accumulate in the body leading to aging.

How Can Free Radical Injury Be Prevented, or What Are Antioxidants?

Free radical injuries can be prevented by stabilizing and removing free radicals in the body. Antioxidants stabilize free radicals by donating extra electrons, thus reducing their damaging property. Antioxidants delays and inhibits the scavenging property of free radicals. Antioxidants terminate the chain reaction created by free radicals, thus protecting the body from oxidative stress. Uric acid, glutathione, and ubiquinol are the antioxidants produced during body metabolism. Antioxidants are also provided to the body through food. Vitamins E, C, and A act as antioxidants and cannot be made by the body. They are supplied in the diet in the form of fruits and vegetables.

What Are the Types of Antioxidants?

There are three types of antioxidants.

• Enzymatic Antioxidants

  • Superoxide Dismutases - These enzymes break superoxide anions into oxygen and hydrogen peroxide. These enzymes are present in the aerobic cell and extracellular fluid.

  • Catalase - It is found in all living organisms exposed to oxygen. It breaks down hydrogen peroxide, a free radical, into hydrogen and water. Catalase is found in high concentrations in the liver.

  • The Glutathione System - It consists of glutathione, glutathione reductase, and glutathione peroxidase. They catalyze the breakdown of hydrogen peroxide and hydroperoxides.

• Non-enzymatic Antioxidants -They consists of vitamin C (ascorbic acid), vitamin E (tocopherol), uric acid, and melatonin.

• Plant-Derived Antioxidant - Whole food, broccoli, carrot, tomatoes, green vegetables, and spices like turmeric, mustard, and ginger.

Conclusion

Free radical injury has been established as one of the many causes of health problems like cardiovascular disease, cancer, cataract, diabetes, atherosclerosis, and asthma. Antioxidants prevent tissue damage by inhibiting the free radical formation and destroying them. Oxidative stress caused by decreased antioxidant activities is linked with various pathological conditions. The body has its antioxidant defense system. However, antioxidants should be taken from external sources to reduce the free radical load. Both natural and synthetic sources of antioxidants are available; however, as synthetic antioxidants have been proven dangerous for health, the search for safe and new natural antioxidant compounds has intensified. Plant-derived dietary components like ginger, turmeric, clove, saffron, etc., are also sources of antioxidants and have gained immense popularity in recent years.