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بسم الله الرحمن الرحيم. (الله الذى خلقكم من ضعف ثم جعل من بعد ضعف قوة ثم جعل من بعد قوة ضعفاً وشيبةً يخلق ما يشاء وهو العليم القدير). صدق الله العظيم الروم ـ 54. I- RADIATION. INJURY. Ionizing radiation. Non-ionizing radiation. Particulate Alpha-, Beta-particles & Neutrons.
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بسم الله الرحمن الرحيم (الله الذى خلقكم من ضعف ثم جعل من بعد ضعف قوة ثم جعل من بعد قوة ضعفاً وشيبةً يخلق ما يشاء وهو العليم القدير) صدق الله العظيم الروم ـ 54
I- RADIATION INJURY
Ionizing radiation Non-ionizing radiation Particulate Alpha-, Beta-particles & Neutrons Non-particulate X- and Gamma-rays Visible light and infra red RADIATION
Direct Indirect Neutron Alpha Macromolecules biomembranes H2O Damaged molecules Free radicals O2 Cell death Superoxides Peroxides Radiation cellular damage X- & gamma rays
Free radicals Molecules Radiolysis of water and free radicals formation .OH H2O2 H. H2 HO.2 O.-2
Hydroxylation Strand breaks Oxidized bases Cross- linkage .OH Phenylalanine O-Tyrosine Peroxidation OH R R Ketones Dialdehydes Alcohols Aldehydes DNA Protein Oxidative damage by free radicals Lipids
LIPID MEMBRANE OXIDATION HO.2 or .OH + LH L. + H2O2 or H2O L. + O2 LOO. LOO. + L`H LOOH + L`. L`. + O2 L`OO. L`OO. + L``H L`OOH + L``. Fe+++ LOOH LO. + Fe+++ + OH- And so on
Free radical theory Proposes that aging is the cumulative result of oxidative damage to the cell’s macromolecules (DNA, lipid, protein) that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: 1- variation in species life span is correlated with metabolic rate and protective antioxidant activity. 2- enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity 3- cellular levels of free radical damage increases with age. 4- reduced calorie intake leads to a decline in the production of reactive oxygen species and an increase in life span.
Erythrocytes fibroblasts protein Protein carbonyl 5 kb deletion Liver and kidney mtDNA mtDNA Rearrangement Skeletal muscle mtDNA Heart mtDNA Brain mtDNA/nDNA 8-OH-dg 8-OH-dg Heart mtDNA mtDNA deletions EVIDENCE OF OXIDATIVE INJURY WITH ADVANCING AGE IN HUMAN
III- PROTECTION AGAINST RADIATION INJURY
Direct DNA strands Damaged molecules Cell death Stem cell depletion Organism death Free radicals Superoxides peroxides H2O O2 Indirect Hydrogen transfer Enzymatic repair Scavenging Hypoxia Antioxidants Detoxification Repopulation Increased survival STRATEGIES FOR REDUCING RADIATION INJURY Neutrons and alpha PROTECTION REPAIR REGENERATION X and gamma rays GENETICS Reduce concentration of reactive intermediates Restore molecular function Stimulate proliferation of surviving stem cells
Antioxidants Aminothiols Eicosanoids Genetic approaches SCAVENGING HYPOXIA Enzymatic Non-enzymatic PROTECTION AGAINST CELLULAR DAAMGE Cysteine analogues Arachidonic acid * Define encoding gene sequences for enzymes involved increasing SOD synthesis * PAF * DiPGE2 * GE2 * LTC4 * Ex. WR compounds * 1/2 hr before irradiation * DRF * Vit. E, A, C, * Minerals:Se * Gluitathione * Melatonin * SOD * GSH-Px * GSH-Rd * Catalase * Define sequence of sensitive sites and targeting protective agents to these sites
H2O Mitochondria P450 oxidases Catalase Fe++ Fe+++ SOD OH-+ .OH H2O2 O.-2 2GSH Lipid peroxidation Glutathione peroxidase Glutathione reductase GSSG H2O ENZYMATIC SCAVENING O2
Free radical chain reaction Extracellular fluid LOOH LOO. Membrane H2O TocOH TocO. Phospholipase A2 HO. O2 LOOH, H2O2 GSH Vit. Coxd GS-SG Vit. Cred GSH Cytosol Glutathione peroxidase Se Catalase SOD .O2 Superoxide H2O LOH GS-SG NON-ENZYMATIC SCAVENING LH
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