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The overwhelming dominance of ROS generated by enzymes like NADPH oxidases and xanthine oxidase over antioxidants like superoxide dismutase causes cell injury and tissue damage through direct injury, lipid peroxidation and protein oxidation leading to protease release and antioxidant and antiprotease enzyme inactivation as well as alteration of transcription factors activator protein-1 and NFκB

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ACKNOWLEDGEMENTS Preparation of this chapter was supported by National Institute of Health grants R01-DK55532 and R01-AA12307