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Redox homeostasis & oxidative stress

Redox homeostasis & oxidative stress. Redox homeostasis & oxidative stress. Redox homeostasis - natural levels of oxidants (O 2 ) and antioxidants in each cell Disruption of redox homeostasis

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Redox homeostasis & oxidative stress

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  1. Redox homeostasis & oxidative stress

  2. Redox homeostasis & oxidative stress Redox homeostasis- natural levels of oxidants (O2) and antioxidants in each cell Disruption of redox homeostasis -> depletion of oxygen: metabolism disruption, acidosis in tissues, cell necrosis rare: INSIDE TUMORS -> overproduction of oxidants: = oxidative stress GENERAL MECHANISM OF TOXICITY

  3. Overproduction of oxidants Oxygen – principal molecule in living organisms Oxygen increases reactive derivatives -> toxicity ROS = Reactive Oxygen Species: Sources - production in mitochondria (byproducts) - redox-cycling (quinones of xenobiotics) - Fenton-reaction (metals) - oxidations mediated via MFO (CYP) - depletion of antioxidants (reactive molecules)

  4. Reactive Oxygen Species (ROS) SOD = Superoxide dismutase

  5. Fenton reaction

  6. Reactive Oxygen Species (ROS)

  7. ROS & mitochondria

  8. Examples of chemical-inducedoxidative stress - Metals: fenton reaction -> OH* - Redox-cycling chemicals:oxy-PAHs - Depletion of GSH: reactive molecules, GST-conjugation, metals: SH oxidation ...

  9. Antioxidant depletionGSH (glutathione)

  10. Biomarkers of oxidative damage (will be discussed later)

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