Generation of Free Radicals – Mechanisms of Cellular Injury

by Richard Mitchell, MD

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    00:01 So, free radicals are generated by the absorption of radiant energy.

    00:05 This is radiation.

    00:06 This is gamma rays and neutrons and everything else.

    00:10 And when they hit water in a cell or a tissue that generates hydroxide radicals and a proton.

    00:17 So, that's how radiation does it's thing.

    00:21 That's how it causes free radical development, which can then affect the genome and we can use it therapeutically to kill cancers.

    00:30 It can also be a cause of cancer by causing mutations.

    00:34 So important that you understand this because it's really important for a lot of other pathology.

    00:39 Interestingly enough, it's part of normal respiration.

    00:42 So as electrons move down the electron transport chain along the way you generate very low levels of superoxide free radicals and hydrogen peroxide and hydroxide free radicals.

    00:55 Interestingly, the older and more senescence the mitochondria becomes the more these that get generated.

    01:02 So the mitochondria age, and we've talked previously about how basically every 10 days you turn it over.

    01:08 If you fail to do that, you've got this kind of geriatric old mitochondria cranking out not so much ATP and a lot of ROS.

    01:17 So that's why we need to turn over mitochondria to regular rate.

    01:21 Metal ions such as iron and copper will also contribute to the generation of oxygen free radicals.

    01:28 That's why hemochromatosis.

    01:31 That's why copper overload states are injurious because they generate reactive oxygen species that will end up causing fibrosis.

    01:43 Free radicals are also generated, not just from oxygen.

    01:46 So at the very beginning, we were talking about things that get metabolized.

    01:51 And carbon tetrachloride, or acetaminophen or a variety of other agents as they get metabolized in various tissues will generate along the way, free radicals of those compounds.

    02:04 So carbon tetrachloride, the liver metabolizes it to carbon trichloride free radical Acetaminophen in too high level will get acetaminophen metabolites with a free radical.

    02:16 So enzymatic catabolism will also generate free radicals and those free radicals with unpaired electrons are just as damaging as reactive oxygen species.

    02:26 We also generate nitric oxide radicals, NO with an unpaired electron, that happens in a variety of inflammatory states.

    02:34 So we have many different ways that we are constantly, normally, generating free radicals.

    02:42 So we know that, the body knows that, evolution knows that, so we have to have a way to get rid of them.

    02:48 We'll come back to that.

    About the Lecture

    The lecture Generation of Free Radicals – Mechanisms of Cellular Injury by Richard Mitchell, MD is from the course Cellular Injury.

    Included Quiz Questions

    1. Enzymatic catabolism
    2. Absorption of radiant energy
    3. Inhibition of the free radical-reducing enzymes
    4. Inflammation-induced generation of nitric oxide radicals
    5. Increased cellular respiration
    1. Oxidative phosphorylation
    2. DNA replication
    3. Protein synthesis
    4. Intracellular movement
    5. Transportation of ions and molecules across the cell membrane

    Author of lecture Generation of Free Radicals – Mechanisms of Cellular Injury

     Richard Mitchell, MD

    Richard Mitchell, MD

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