l-h" supply of oxygen is absolutely essential I for the existence of higher organisms. As the saying goes too much of even the best is bad. Very high concentrations of 02 are found to be toxic, and can damage tissues. The present day concept of oxygen toxicity is due to the involvement of oxygen free radicals or reactive oxygen species (ROS). In fact, the generation of reactive metabolites of 02 is an integral part of our daily life. A free radical is defined as a molecule or a mof ecular species that contains one or more unpaired electrons, and is capable of independent existence. Types of free radicals Oxygen is required in many metabolic reactions, particularly for the release of energy. During these processes, molecular O2 is completely reduced, and converted to water. However, if the reduction of 02 is incomplete, a series of reactive radicals are formed, as shown in the next column. r,r,.. (Molecular orygen) re- Y O, (Superoxide) h€,2H+ J H rO, (Hydrogen peroxide) l. e-,H' Hzo+1 + OH- (Hydroxyl radicat) h e-'H* + ,-r,r'(Water) Besides the above (O2, H2O2, OH-), the other free radicals and reactive oxygen species of biological importance include singlet oxygen (1O2), hydroperoxy radical (HOO-), lipid peroxide radical (ROO-), nitric oxide (NO-) and peroxyn itrite (ONOO-). The common characteristic features of free radicals are listed . Highly reactive o Very short half-lifeCan generate new radicals by chain reaction Cause damage to biomolecules, cells and tissues Free radicals and reactive oxygen species (ROS)-not synonymous : By definition, a free radical contains one or more unpaired electrons. e.g. Or, OH-, ROO-. There are certain non- radical derivatives of 02 which do not contain unpaired electrons e.g. H2O2, 102. The term reactive oxygen species is used in a broad sense to collectively represent free radicals, and non- free radicals (which are extremely reactive) of the biological systems. However, most authors do not make a clear distinction between free radicals and ROS, and use them inter- changebly. SOURCES AND GEI{ERATION OF FREE RADICALS The major sources responsible for the generation of free radicals may be considered under two categories l. Due to normal biological processes (or cellular metabolism). ll. Due to environmental effects. It is estimated that about 1-4o/o of the 02 taken up by the body is converted to free radicals. A summary of the sources for generation of free radicals is given in the Tahle 34.1 , and a couple of the processes are briefly described. Lipid peroxidation Free radical-induced peroxidation of membrane lipids occurs in three stages-initiation, propagation and termination Initiation phase : This step involves the removal of hydrogen atom (H) from polyunsaturated fatty acids (LH), caused by hydroxyl radical LH + OH- -----+ L- + H2O Propagation phase : Under aerobic conditions, the fatty acid radical (L-) takes up oxygen to form peroxy radical (LOO-). The I Cellular metabolism . Leakage of electrons lrom the respiratory chain (ETC). . Productionf HrO, or O, by oxidase enzymes (e.9. xanthine oxidase, NADPH oxidase). . Due to chain reactions ofmembrane lipid peroxidation. . Peroxisomal generation of O, and HrOr. . During the synthesis ofprostaglandins. . Productionf nitric oxide from arginine. . During the course of phagocytosis (as a pad of bactedcidal action). . In the oxidation ofheme to bile pigments. . As a result of auteoxidation e.g. metal ions [Fd*, Cu2*]; ascorbic acid, glutathione, flavin coenzymes. II Environmental effects . As a result of drug melabolism e.g. paracetamol, halothane, cy{ochrome P* rehted reactions. . Due to damages caused by ionizing radiations (e.9. X-rays) on tissues. . Photolysis of O, by light. . Photoexcitation of organic molecules . Cigarette smoke contains free radicals, and trace metals that generate OH-.Alcohol, promoting lipid peroxidation.