Redox homeostasis
& oxidative stress


Redox homeostasis & oxidative stress
lRedox homeostasis
- natural levels of oxidants (O2) and antioxidants in each cell
l
lDisruption of redox homeostasis
l
l-> depletion of oxygen: metabolism disruption, acidosis in tissues, cell necrosis
 rare: INSIDE TUMORS
l
l-> overproduction of oxidants:
 = oxidative stress
GENERAL MECHANISM OF TOXICITY

Overproduction of oxidants
lOxygen – principal molecule in living organisms
lOxygen increases reactive derivatives -> toxicity
l
lROS = Reactive Oxygen Species: Sources
l - production in mitochondria (byproducts)
l - redox-cycling (quinones of xenobiotics)
l - Fenton-reaction (metals)
l - oxidations mediated via MFO (CYP)
l - depletion of antioxidants (reactive molecules)

Reactive Oxygen Species (ROS)
SOD = Superoxide dismutase


C:\Documents and Settings\Ludek Blaha\Obrázky\1.gif
Fenton reaction


Reactive Oxygen Species (ROS)






ROS & mitochondria
C:\Documents and Settings\Ludek Blaha\Obrázky\1.gif


Examples of chemical-induced
oxidative stress
l
l- Metals:
l fenton reaction -> OH*
l
l- Redox-cycling chemicals:
oxy-PAHs
l
l- Depletion of GSH:
l reactive molecules,
GST-conjugation,
metals: SH oxidation ...
l
C:\Documents and Settings\Ludek Blaha\Plocha\E3.GIF

Antioxidant depletion
GSH (glutathione)


Biomarkers of oxidative damage
(will be discussed later)