Lecture 20: Free Radicals and Cell Death

Question 1

Give me a bit of a down lo on free radicals and cell death

Answer 1

Firstly a free radical is a cell with one unpaired electron in outer orbit so is highly reactive

Production of oxygen free radicals is a natural consequence of aerobic metabolism and they are constantly generated in vivo by chemical reactions and metabolic processes. Antioxidant defence systems scavenge and minimise the formation of oxygen-radical-derived biochemical products, however, these defences are not completely effective even under normal physiological conditions. In pathologic situations, oxygen free radicals can be generated in excess of a cell’s antioxidant capacity resulting in severe damage to cellular constituents including proteins, DNA and lipids. The inherent biochemical and physiological charateristics of the brain, including high lipid concentrations and energy requirements, make it particularly susceptible to free radical mediated insult

Question 2

What are some common free radicals?

1. Reactive Oxygen species/ intermediates (ROS)
2. Reactive Nitrogen species (RNS)
3. Xenobiotics, drugs, pollutants

Answer 2

1. ROS/ROI (Reactive Oxygen Species/Intermediates)
   - Singlet oxygen 1O2
   - Superoxide anion -radical O2-
   - Hydrogen peroxide -H2O2
   - Hydroxyl radical OH

RNS (Reactive Nitrogen Species)

• Peroxynitrite, ONO2-
• Nitrogen dioxide NO2, -nitric oxide NO
• Dinitrogen trioxide, N2O3

Xenobiotics, drugs, pollutants:
Mycotoxins, halothane, paraquat, paracetamol etc.

Question 3

What is the effect of free radicals?

Answer 3

1) Damage mbs by lipid per oxidation (chain reaction)-affects permeability, secretion and ion transport
2) Cause nucleic acid breaks, base modification and mutations. Cancerogenesis!
3) Attack proteins e.g. polymerisation and inhibits function

Free radicals are hunting for electron to stabilise their position while while oxidising (gives O2?) surrounding molecules

Question 4

What are easily available targets of ROS? reactive Oxygen Species

Answer 4

The cell membrane–> Free-radical caused membrane damage

Question 5

What are physiological LPO reactions?

Answer 5

-electron transport chain
-aging
-myelo-peroxidase activity in phagocytes
-melanin formation
-wound healing
etc

Question 6

What are Pathological LPO-mediated processes?

Answer 6

• Inflammation
• carcinogenesis
• atherosclerosis
• Ischaemia-reperfusion
• alcoholic liver disease
• uraemia
• parkinsons etc

Question 7

Reperfusion Injury

36

Answer 7

Reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than restoration of normal function.

Question 8

Antioxidants
are?
definition?

Answer 8

• An antioxidant is a substance that when present in low concentrations relative to the oxidizable substrate significantly delays or reduces oxidation of the substrate (Halliwell, 1995).
• Chemically antioxidants are different molecules inhibiting the action of free radicals/prooxidants
• During its reaction the antioxidant sacrifices itself by becoming oxidized.

Question 9

How do you group antioxidants?

Answer 9

-enzymatic- non enzymatic
-water-soluble-lipid soluble
-natural-artificial
Enzymatic defence is stronger in ICF than in ECF
Chemical, non-enzymatic reactions are common in ECF

Question 10

Check out table of antioxidant defence on slide 19

Answer 10

might need to watch this or something

Question 11

What is a chemical antioxidant and what does it do?

Answer 11

A chemical antioxidant acts by donating an electron to a free radical and converting it to a nonradical form. However, this
defense is like a double-edged sword….