1. Free Radicals: Injury induced by free radicalsO2

2. (1) Free radical
Free radical——atoms, molecules or ions with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions.
Oxygen free radical
Lipid radical

3. (2) Oxygen free radical, OFR
Types：
the superoxide anion (O2-)
the hydroxyl radical (OH ·)
singlet oxygen (1O2 )
hydrogen peroxide (H2O2)

4. (3) Lipid free radicals：
The interaction of oxygen free radicals with polyunsaturated fatty acids in the phospholipids of cell membrane leads to the formation of lipid free radicals.
Types：
Fatty acid radical (L·)
Lipid peroxide（LOO·）
(4) Others: Cl·, CH3·, NO·
氧化还原过程中产生的具有高活性的一系列中间产物

5. (5) Generation and elimination of oxygen free radicals
1) Origin of O·-2：
a. Mitochondria
b. Oxidation of some chemicals in body.
c. Catalysis by enzymes
d. Stimulation of cells with toxins

6. O2  SOD (6) Generation of OFR O2 + e Cytaa3 O2 + 3 e + 3H+ 2 H2O
HO + H2O
H2O2
Cytochrome aa3
2 H2O
O2 + 4 e + 4H+
SOD, Superoxide dismutase

7. Haber-Weiss reaction (without Fe3 )
O2－ + H2O O2 + OH +OH 
SLOW
hydroxyl radical; ferrum

8. Fenton-Haber-Weiss reaction
O2－ + H2O O2 + OH +OH 
FAST

9. Cysteine, Vit C, glutathione
(6) Elimination of oxygen free radicals
1）Small MW scavenging agents
Dihydrocoenzyme II
Cysteine, Vit C, glutathione
Vit E、 Vit A

10. 2）Enzymatic scavenging agents
Catalase (CAT)
Superoxide dismutase
MnSOD
CuZnSOD
Peroxydase （H2O2）

11. (7) The mechanisms of increased generation of oxygen free radicals during ischemia-reperfusion

12. 1) Mitochondria pathway
Ca2+entering MT
O2+e↑
Mn− SOD + O Mn+ − SOD + O2
O-2↑
Hypoxia Mn-SOD 
Superoxide dismutase
Pm O2 呼吸链受抑 NADH蓄积供电子

13. 2) Xanthine oxidase pathway
Xanthine oxidase (XO) 10%
Xanthine dehydrogenase (XD) 90%
Ca+2

14. Effect of XO on formation of OFR
Ischemia:
ATP comsumption↑
Hypoxanthine ↑
(1) Ca2+ overload→
activating protein kinase O2
Reperfusion:
xanthine + O·-2+ H2O2 XD XO
(2) Restoration of O2
supply O2
O·-2+ H2O2 +Uric acid
Effect of XO on formation of OFR
OH ·

15. H+ + O-2·+H2O2 3) Neutrophil pathway NADH(I) NADPH(II) + O2 Activating
C3, LTB4
(Complement C3
Leukotriene B4 )
Hexose shunt activity↑
cellular respiration ↑
NADH oxidase
NADH(I)
NADPH(II)
H+ + O-2·+H2O2 
+ O2
NADPH oxidase

16. 4) Catecholamines  Adr Remove O-2· adrenochrome Methyl transferase
vanillylmandelic acid (normal)
monoamine oxidase
Stress 80% O2
Remove
O-2·
adrenochrome

17. (8) Alterations induced by OFR
1) lipid peroxidation
Alteration of membrane lipid
Function inhibition of membrane proteins
Enhance of arachidonic acid metabolism
Blockage of ATP production in mitochondria membrane
4造成生物膜损害

18. 2) Injury of chromosome and nuclear acid
80% induced by OH

19. Destructive effects of OFR:
Attacking membrane structure such as mitochondria membrane  interfering with energy metabolism
Attacking DNA  changing genetic information  cell death
Initiating lipid peroxidation  increasing permeability of membrane and inducing destruction of membrane  cell death
Destroying proteins  decreased enzyme activity  metabolic disorder