Mechanism of inactivation of free radicals

Free radicals produced within the body can be inactivated by the following ways

• Antioxidants: Antioxidants either block the initiation of free radical formation or inactivate free radicals and terminate radical damage. Example: Vit-A, Vit-E, Vit-C, Glutathion.
• Iron copper can catalyze the formation of reactive oxygen species. The levels of these reactive forms are minimized by binding of the ions to storage and transport proteins (Transferrin, Ferritin, Lactoferrin and ceruloplasmin) thereby minimizing OH formation.
• A series of enzymes acts as free radical scavenging systems and breakdown hydrogen peroxide and superoxide anion. Example:
• Catalase
• Superoxide dismutases
• Glutathion peroxidase 

Classification of free radicals.

Free radicals can be classified as:

• Reactive oxygen species
• Superoxide anion
• Hydrogen Peroxide (H2O2)
• Hydroxyl radical (OH)
• Hypochlorous acid (HOCl)
•  Reactive nitrogen Species:
• Nitric oxide (NO)
• Peroxynitrite anion (ONOO)

Role of free radicals in cell injury OR mechanism of cell injury by free radicals.

The effects of reactive oxygen species are wide ranging, but three reactions are particularly relevant to cell injury:

1. Lipid peroxidation of membrane: Free radicals in the presence of oxygen may cause peroxidation of lipids within plasma and organellar membrane
2. Oxidative Modification of protein: Oxidative modification enhances degradation of critical proteins by the multicatalytic proteosome complex, raising havoc throughout cell.
3. Lesions in DNA: Reactions with thymine in nuclear and mitochondrial DNA produce single stranded breaks in DNA.   

Mechanism of production of free radicals.

The following mechanisms are involved in production of free radicals.

1. Absorption of radiant energy
2. Enzymatic metabolism of exogenous chemicals or drugs
3. The reduction-oxidation reactions that occur during normal metabolic process
4. Re-perfusion injury
5. Oxygen Toxicity  

What are free radicals?

Free radicals are chemical species that have a single unpaired electron in an outer orbit.

Reduced reactive oxygen forms are produced as an unavoidable byproduct of mitochondrial respiration. Some of these forms are free radicals

Describe the effects of cellmembrane damage.

Plasma membrane damage results in loss of osmotic balance and influx of fluids and ions as well as loss of proteins, enzymes, co-enzymes and ribonucleic acids. The cells may also leak metabolites, which are vital for the reconstitution of ATP thus further depleting net intracellular high energy phosphates. Injury to lysosomal membranes results in leakage of their enzymes into the cytoplasm and activation of these enzymes. Activation of these enzyme leads to enzymatic digestion of cell components resulting in loss of ribonucleoprotein, deoxyribonucleoprotein and glycogen and the cells die by necrosis.

What are the common causes of cell injury?

The common causes of cell injury are as follows:

• Oxygen deprivation

• Hypoxia

• Physical agents
• Mechanical Trauma
• Extremes of temperature
• Sudden changes in atmospheric pressure
• Radiation
• Electric shock

• Chemical agents and drugs:
• Oxygen in high concentration
• Arsenic
• Cyanide
• Mercuric salt
• Insecticides
• Carbon-mono-oxide
• Asbestos

• Infectious agents:
• Virus, Bacteria, Fungi, Helminths, Rickettsiae

• Immunological reactions
• Genetic derangements
• Nutritional imbalance

Describe The Biochemical Mechanism Leading To Cell Membrane Damage

The following biochemical mechanism contribute to cell membrane damage:
A. Mitochondrial dysfunction- Defective mitochondrial function results in decreased phospholipid synthesis, which affects all cellular membrane. At the same time increase cytosolic Ca++ activate phospholipases and leading to breakdown of phospholipids. The net result is a depletion of phospholipids from the mitochondria and other dellular membranes and accumulation of free fatty acids. In the mitochondria this changes causes permeability defects.

B. Loss of membrane phospholipids: This is because activation of endogenous phospholipases by increased levels of cytosolic calcium, phospholipid loss can also occur secondary to decreased ATP-dependant reacylation or diminished de novo synthesis of phospholipids.

C. Cytoskeletal abnormalities: Activation of proteases by increased cytosolic Calcium may cause damage to elements of the cytoskeleton.

D. Reactive oxygen species: Partially reduced oxygen free radicals cause injury to cell membranes and to other cell constituents.

E. Lipid breakdown products: These includes unestirified free acids, acyl carnitine and lysophospholipids catabolic products that are known to accumulate in injured cells as a result of phospholipid degradation. They have detergent effect on membrane.