The Unified Concept
of
Oxidative Stress
Pr A. Avignon
Service des
Maladies
Métaboliques
Hôpital Lapeyronie
Montpellier
Pr A. Avignon, MGSD, Istambul 04/2007
The Unified
Concept of
Oxidative
Stress
Oxidative
Stress
Pr A. Avignon, MGSD, Istambul 04/2007
What is
Oxidative
Stress ?
OXIDANTS
Oxygen Free Radicals
Nitrogen Free Radicals
ANTIOXIDANTS
Specific Enzymes
Vitamin E, Vitamin C,
Carotenoids, Selenium
Pr A. Avignon, MGSD, Istambul 04/2007
Free
Radicals

Any molecule containing one or
more unpaired electrons

Reactive Oxygen Species (ROS) -

Reactive Nitrogen Species (RNS) - NO

.
Reactive Metabolites or Intermediates
- metabolic activation of drugs, toxins,
pollutants, cigarette smokes, etc.
Pr A. Avignon, MGSD, Istambul 04/2007
Reactive
Oxygen
Species
(ROS)



Superoxide (O2.-)
Hydrogen Peroxide (H2O2)
Hydroxyl Radical (OH.) - product of
Fenton reaction catalyzed by free Fe and Cu

Singlet Oxygen (1DgO2) - oxygen at an
excited state, requiring photosensitizers and
photons
Pr A. Avignon, MGSD, Istambul 04/2007
Sources of
oxygen free
radicals
Pr A. Avignon, MGSD, Istambul 04/2007
Free Radical
Defense
System
Pr A. Avignon, MGSD, Istambul 04/2007
Oxidative
Stress:
Consequences
Pr A. Avignon, MGSD, Istambul 04/2007
Obesityinduced
oxidative
stress
Pr A. Avignon, MGSD, Istambul 04/2007
Fatty Acids Induced
Oxidant
Stress
J Clin Endocrinol Metab 81:4244-4248, 1996
Pr A. Avignon, MGSD, Istambul 04/2007
ObesityInduced
Oxidant
Stress and
Insulin
Resistance
Muscle Cells
Pr A. Avignon, MGSD, Istambul 04/2007
ß-Cell
Toxicity, and
Oxidative
Stress in
Type 2
Diabetes
Role of ß-cell mitochondria in sensing
increases in plasma glucose and inducing
insulin secretion.
Green K et al, Diabetes 53 (Suppl. 1):S110, 2004
Pr A. Avignon, MGSD, Istambul 04/2007
ß-Cell
Toxicity, and
Oxidative
Stress in
Type 2
Diabetes
Diabetes 53 (Suppl. 1):S119–S124, 2004
Pr A. Avignon, MGSD, Istambul 04/2007
ß-Cell
Toxicity, and
Oxidative
Stress in
Type 2
Diabetes



Sensibility to oxidative stress
Oxidative stress increased by FFA
FFA acids and oxidative stress
induce apoptosis of B-cells
Diabetes 53 (Suppl. 1):S119–S124, 2004
Pr A. Avignon, MGSD, Istambul 04/2007
Hyperglycemia /
Oxidant Stress /
Diabetic
Complications
Extra-cellular glucose
GLUT-1
Kidney
Retina
Neurones
Hexokinase
Glucose-6-P
Phosphohexo
isomérase
Fructose-6-P
Cycle de
Acetyl CoA
Krebs
PDH
pyruvate
Glyceraldéhyde-3-P
1,3-Diphosphoglycérate
Pyruvate
Pr A. Avignon, MGSD, Istambul 04/2007
Hyperglycemia
Oxidative Stress
Diabetic
Complications
Glucose extra cellulaire
Voie des
Polyols
Hexokinase
Glucose-6-P
Phosphohexo
isomérase
Fructose-6-P
Voie des
Hexosamines
Voie de la
Protéine Kinase C (PKC)
Glyceraldéhyde-3-P
Voie des Produits Terminaux
de la Glycation
1,3-Diphosphoglycérate
Pr A. Avignon, MGSD, Istambul 04/2007
Hyperglycemia
/ Oxidative
Stress / Diabetic
Complications
International Journal of Obesity (2006) 30, 400–418.
Pr A. Avignon, MGSD, Istambul 04/2007
Hyperglycemia /
Oxidative Stress
/ Diabetic
Complications
Nature 404, 787 - 790 (2000)
Pr A. Avignon, MGSD, Istambul 04/2007
Conclusion
Oxidative
Oxidative
Stress
Stress
Pr A. Avignon, MGSD, Istambul 04/2007
Merci
Pr A. Avignon, MGSD, Istambul 04/2007