Generation of Free Radicals – Mechanisms of Cellular Injury

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.