Free radical injury (HY)
- What is free radical?
• Atoms or molecules with unpaired electron in outer orbit - Give example of physiologic and pathologic free radical?
Physiologic - in oxidative phosphorylation, when oxygen receives 1, 2 or 3 electron, it’s partially
reduced and creates superoxide (O2.), hydrogen peroxide (H2O2), and hydroxide(.OH) free radical
respectively. Only if O2 receives 4 electron, it becomes water. Of all free radicals, hydroxide free
radical is most damaging (HY).
•
Oxygen ----(accept 1 electron)-----> Superoxide (.O2) ----(accept 1 electron)-----> Hydrogen
peroxide (H2O2) ----(accept 1 electron)-----> Hydroxide (.OH) ----(accept 1 electron)-----> Water
(H2O)
ionizing radiation (creates hydroxide radical .OH),
inflammation (in neutrophils, O2 is converted to superoxide by NADPH oxidase)
Metals - iron and copper. Hemochromatosis and Wilson disease are disease of Fe and
Cu accumulation in body - creation of free radicals are main way that the disease
affect us. (Fenten reaction - reaction by which Fe generates hydroxide free radical
(HY))
Drugs and chemicals - acetaminophen, carbon tetrachloride. High dose of
acetaminophen causes liver necrosis by free radical generation
Thyroid hormones increase free radical formation
• Pathologic - - How do free radicals harm the cell?
• Oxidation of DNA (lead to fast aging and cancer) and oxidation of proteins
• Peroxidation of lipids - What are 3 mechanism of removal of free radicals? Give example of 3 enzymes.
• Antioxidants - vit K
• Metal carrier proteins - transferrin, ferretin
○ Superoxide dismutase (gets rid of superoxide)
Catalase ( gets rid of hydrogen peroxide)
○ Glutathione peroxidase (get rid of hydroxide free radical)
• Enzymes (HY) - Give example of 2 free radical injury? (HY)
Carbon tetrachloride (dry cleaning chemical)- CCl4 is converted to CCl3 (radical) by Cyp 450 in
liver. It causes reversible damage to hepatocytes - cell swells --> swelling of RER causes ribosomes
to fall off and apolipoprotein synthesis goes down --> liver can’t repackage and send fat away -->
fatty liver disease (VHY)
•
1.4 Free radical injury (HY)
Cellular injury Page 4.1
Fig - T represents fat in hepatocyte; a hepatocyte is shown in circle
Reperfusion injury - During reperfusion of ischemic organ, immune cells will attack the dead tissue
in presence of oxygen which will generate free radicals. More injury ensues. Classic example is
blood troponin continuing to rise after reperfusion of heart after MI.