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Oxidative stress - Oxidative stress in health and disease...

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1 s Oxidative stress in health and disease Current role of antioxidants in lung diseases Dr. Alok Nath Department of Pulmonary Medicine and Critical Care PGIMER Chandigarh Where to start…… Questions arising in our minds ??? What are free radicals ? What are reactive oxygen species ? How do they cause injury ? What are the consequences ? What are the defense mechanisms ? etc etc etc….
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2 Basics of oxidative stress What are free radicals Any species capable of independent existence that has one or more unpaired electrons Free radicals are highly unstable and reactive Stability can only achieved when they these electrons get paired Superoxide ion O 2 Hydroxyl radical OH Basics of oxidative stress
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3 Basics of oxidative stress Oxygen radicals vs reactive oxygen species. A radical may donate or accept electron becoming either a reducing or oxidizing radical Reactions of free radicals proceed as chain reactions Basics of oxidative stress Reactive oxygen species (ROS) - oxygen radicals and certain non radical oxidizing agents. Major oxygen radicals are ; Superoxide Hydroxyl Peroxyl Hydroperoxyl Nitric oxide Nitrogen dioxide
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4 Basics of oxidative stress And reactive oxygen species are Hydrogen peroxide Hypochlorous acid Ozone How do the free radicals react ? Radical + Radical (pairing of electrons) A + A A – A Radical + Non-radical (transfer of electrons) A + B A + B chain reaction………. FeS N-1, N-3, N-4 H + FeS N-2 FMN cyt c III CuB a a 3 Q 0 Q i b b FeS C 1 SDH cyt c CoQ Reactive Oxygen species and the Respiratory Chain NADH Succinate Complex I Complex II Complex III Complex IV O 2 O 2 - H 2 O 2 SOD2 . OH- Fe 2+ IMS SOD1 H 2 O 2 O 2 O 2 - MATRIX
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5 Basics of oxidative stress Oxidative stress; implicated in various diseases. Why lungs?? exposed to higher concentrations of O 2 Larger surface area (approx. 100 m 2 ) Oxidants play imp. role in various pulmonary disorders BPD Asthma COPD Fibrosing alveolitis ARDS Bronchogenic carcinoma Basics of oxidative stress ROS are produced in vivo in Mitochondria to produce ATP by oxidative phosphorylation Macrophages and neutrophils to kill bacteria Reactions involved in cell signaling Most important are the reaction catalyzed by NADPH ( Nicotinamide dinucleotide phosphate) XOR ( Xanthine oxidoreductase) MPO ( Myeloperoxidase )
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6 Basics of oxidative stress Major exogenous sources of ROS are Air pollution Tobacco smoke Toxic wastes Sunlight Radiation Basics of oxidative stress Superoxide Most reactive oxygen metabolite Generated in mitichondrial NADH dehydrogenase and the ubiquinone Q cytochrome B complex Microsomal and nuclear membrane cytochromes Cytoplasmic enzymes like Xanthine oxidase Activated inflammatory cells Endothelial cells Spontaneously dismutates or scavenged by antioxidant mechs.
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7 Basics of oxidative stress Hydrogen peroxide More stable than superoxide - mitochondria, cytoplasm and endoplasmic reticulum through enzymatic and non enzymatic dismutation Other enzymes like peroxisomal oxidases such as D-amino oxidase, urate oxidase and fatty acyl CoA oxidase.
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