Free Radical Induced Cell Injury

                                       Cell Injury

Free radical induced Injury

Free radicals are chemical species that have a single unpaired electron in outer orbit. Free radicals initiate autocatalytic reaction.
It is mainly occur in reperfusion of the ischemic cell. There are many more causes like chemical injury, cellular aging, hyperoxia, killing of exogenious biological agents, destruction of tumor cells, inflammatory damage, chemical injuries, ionization, artherosclerogenesis.

There are some radicals, like superoxide radicals, hydroxyl ions, peroxide ions, very destructive to cells which cause lipid peroxidation, oxidation of protein, DNA damage, cytoskeleton damage etc.

Free radicals may be initiated with in cells by enzymatic reactions and nonenzymatic systems. Different cause for initiation of free radical-

• Absorption of radiant energy.
• Enzymatic metabolism of chemicals or drugs. For ex, carbon tetrachloride can generate [CCl3]* which cause autooxidation of the polyenic fatty acid present within membrane phospholipids.
• Some metals which accept or donate e-. For ex, Cu & Fe (Fenton reaction).
• Nitric Oxide (NO) can act as a free radical and converted into highly reactive peroxynitrate anion (ONOO-) as well as NO2* and NO3 -. Normally, NO can be produced by endothelial, neurons, macrophages etc.

The redox reactions occur during normal metabolism. For ex, in respiration, molecular oxygen is reduced to water by accepting 4 electrones. During this process small amount of toxic intermediates are formed.


Free radical reaction can be studied as follows:

   1. Lipid Peroxidation: Polyunsaturated fatty acid of membrane is attacked repeatedly by free radicals to form highly destructive polyunsaturated fatty acid (PUFA) radicals like lipid hydroperoxy radicals and lipid hypoperoxides. This is termed as lipid peroxidation. These lipids are widely spreaded to other part of membrane that is lipid peroxidation takes place at adjoining part of membrane causing damage to entire cell membrane.

   2. Oxidation of protein: Free radical causes CI by oxidation of protein macromolecules of cell causing cross linkage in the amino acid sequences of protein and fragmentation of polypeptides.

   3. Effect on DNA damage: Free radical breaks DNA fragments to single strand, so there will be formation of DNA which is defective. Replication of this DNA is not possible and there by cell death may occur.

   4. Cytoskeleton Damage: Free radicals interfere with mitochondrial aerobic phosphorylation and decreases synthesis of ATP leading to cytoskeleton damage.

 

There are certain anti-oxidants present endogenously to fight against these oxidative free radicals like Vitamin-E, sulphahydral containing substances like cystine, SOD, catalase, GTH & serum proteins like ceruplasmin and transferin.