1.4 Free Radical Injury

Question 1

How are free radical produced physiologically?

Answer 1

During oxidative phosphorylation: cytochrome C oxidase (complex IV) transfers electrons to O2
Partially reduction of O2 leads to generation of Superoxide, Hydrogen peroxide, hydroxyl
These are the molecules created by O2 receiving 1,2,3 electrons instead of the 4 needed to make H2O

Question 2

How are free radicals produced in ionizing radiation?

Answer 2

water hydrolyzed to hydroxyl (OH-)

Question 3

Which of the ROS is the most damaging?

Answer 3

OH-

Hydroxyl

Question 4

How does inflammation create free radicals?

Answer 4

Neutrophils take O2 and with NADPH oxidase convert it to O2-
(and superoxide dismutase converts it to H2O2 which can then be converted to bleach by myeloperoxidase)

Question 5

How do metals create free radical?

Answer 5

Copper and Iron
Fenton reaction from Fe2+
In hemochromatosis and Wilson’s disease the underlying cause of damage is the creation of free radicals by high levels of these metals

Question 6

By what mechanism does acetaminophen cause liver damage?

Answer 6

Conversion by the P450 system creates free radicals that damage the liver

Question 7

Why are free radicals bad, or how do they cause damage in the body?

Answer 7

Peroxidation of lipids and oxidation of DNA and proteins

DNA damage causes aging and oncogenesis

Question 8

What are the 3 main ways the body can eliminate free radicals?

Answer 8

Antioxidants: glutathione, Vit A, C, E
Enzymes: superoxide dismutase, glutathione peroxidase, catalase
Catalase: in peroxisomes

Question 9

How does the body get rid of OH-?

Answer 9

Glutathione peroxidase

Question 10

What free radical is classically found in the dry cleaning industry?

Answer 10

Carbon Tetrachloride

CCl4

Question 11

What is the classic finding from Carbon Tetrachloride poisoning?

Answer 11

Fatty liver resulting from free radical damage of hepatocytes that causes cell swelling and decreased protein synthesis including apolipoproteins which prevents the liver from being able to export lipids so they accumulate

Question 12

Explain reperfusion injury

Answer 12

Return of blood to damaged tissue results in return of O2 and inflammatory cells, both leading to an increase of free radicals and oxidative damage
This explains the continued rise of troponin and other cardiac enzymes after reperfusion of infarcted myocardial tissue