Sources of oxidative stress in human pathophysiology
| Source | Mechanism |
| Mitochondrial electron transport | Leakage of superoxide due to inefficient reduction of O2 |
| Transition metal icons | Cu and Fe facilitate hydroxyl radical formation |
| Inflammation | Free radicals released by activated phagocytes |
| Enzymes eg. Xanthine Oxidase | Release superoxide during reperfusion of ishemic tiss |
| Drug metabolism. eg. Paracetamol | Free radical intermediates created during metabolism |
| Cigarette smoke | Gas phase rich in free radicals |
| Radiation | X-rays, UV light |
Diseases associated with increased oxidative activity implicated in the pathophysiology:
| Atherosclerosis | Ishemica reperfusion injury |
| Diabetes | Inflammation-Rh arthritis -Infl bowel dis -pancreatitis |
| Cancer Neurological dis: -stroke -parkinson’s dis -trauma |
Hypertension Hyponia Sepsis |
Ocular
dis: Cataract
Idiopath Pul fibrosis
Neonatal resp distr syndr
Cystic fibrosis
Aids,Hematological disExercise.
Increased quantities of oxidized metabolites of theses molecules have been detected in patients with a variety of diseases and although a rich array of natural antioxidant mechanisms exit to prevent or retard oxidation, it is often found to be inadequate in many of these diseases.
Cell Membranes:
Polyunsaturated fatty acids with in the cell membrane are particularly suspectible to oxidative attack (lipid peroxidation), often result in metal ion-dependent OH radical formation. If O2 is present, long chains lipid peroxides may be formed by a rapid free radical chain reaction causing serious disruption of cell membrane function. Hydroperoxides form polyunsaturated fatty acids of membrane phopholipids are reduced by glutathione peroxidase, either directly or after releases of these peroxides in cytosol by phospholipase.
Proteins:
Proteins exposed to free radicals may fragment, cross link or aggregate, the consequences of which include interference with ion channels, failure of cell receptors and failure of oxidative phosphorylation. Free radical induced damage to DNA may cause destruction of bases and deoxy-ribose sugars or single or double strand breaks. Free radicals induce in proteins an accumulation of carbonyl groups that can be evaluated after condensation with 2,4 dinitro phenyl hydrazinc for evaluation. The DNA of a cell undergoes about 10,000 radical attacks each day and more than 12 different metabolits produced out of which Thymidine glycol (TG) and 8 hydoxy-2 ‘-deoxy guanosine can be used as Markers.
It is now demonstrated, both in procaryocates and eucaryocytes, that specific enzymes repair the damages DNA, by a direct or an indirect process and involves glutathione transferases and peroxidases in the former and RNA glycolas in the latter. The term of “Redoxyendonuclases” has been proposed for all nucleases that are involved DNA repair, by allowing excision of oxidized nucleotides and bases.
