Toxicity of oxygen
Oxygen (O2) is a vital
resource for most
2.5 billion years ago, the
increase of the
concentration of oxygen
due to photosynthetic
microorganisms allows a
widespread of life on earth.
O2 is a very powerful oxidizing agent, thus reactions with organic
compounds are potentially very energetic.
In spite of that, O2 itself is not dangerous, because it is not reactive enough.
However, incomplete oxidation produces reactive and energetic byproducts
(Reactive Oxygen Species or ROS). ROS are very toxic chemicals.
– They are involved in the general mechanism of oxidative stress, in particular in
– They are so toxic that they are used in a immune mechanism to kill bacteria.
Incomplete reduction of oxygen
produces damaging free radicals
Incomplete reduction in mitochondria Cascade reaction
Cellular respiration relies on the
transfer of electrons in redox
reactions in the membrane of
mitochondria to produce energy.
O2 is the final acceptor of electrons.
O2 + 4e- + 4H+ H2O
Incomplete reduction of oxygen leads °O2- reacts in the organisms to produce
to the formation of the anion very reactive free radicals (HO°, nitrogen
superoxide °O2-. radical), thanks to the help of catalyzing
O2 + e- °O2- metals (e.g. iron found in hemes).
Ubiquitous phenomenon that
happens all the time in every cell.
Toxicity of Reactive Oxygen
Reactivity and Targets Effect on the organism
°O2- Rather low reactivity. Phospholides in Impedes with the permeability
Can cross membranes. membranes. of membranes.
°O2- is a precursor of more
H202 Low reactivity. Toxicological data:
Easily degraded in HO° (with LD50 between 630 and 7500
metals or sunlight). mg/kg depending on animals.
It is impossible to have Chronic exposure results in
toxicological data for free radicals lesions in all tissues, particularly
(they are too reactive) but not for in the liver, the kidney and in the
HO° Extremely reactive with all All proteins. Accumulation of unrepaired
(and all organic compounds. Membranes. damages in all tissues.
free Reacts as soon as it is DNA (mutations, Ultimately, it can provoke the
radicals) produced. alteration of its death of cells by apoptosis (if the
replication). alteration of DNA is too severe).
Effect of the oxidative stress:
Free Radical Theory states that Defensive mechanisms against the
ageing is the result of the oxidative oxidative stress
Free radicals are naturally produced
throughout the body.
ROS are a cause for the
accumulation of unrepaired damage
in the tissues.
Increase of antioxidants in the
organism should theoretically Antioxidants like vitamins A, C, E
increase the life expectancy but there neutralize free radicals and limit the
is no strong evidence. oxidative stress.
Super Oxide Dismutase (SOD) and
catalase enzymes safely degrade ROS,
thus limiting the effect of oxidative
stress on the organism.
They are very important enzymes,
particularly abundant in metabolically
active tissues (e.g. in the liver).
Use of the oxidative stress in
Some enzymes like NADPH
oxidase catalyse the production of
Reactive Oxygen Species (°O2-).
They are found mainly in
phagocytes because they are
involved in a respiratory burst.
The production of free radicals in
high concentrations is deadly for
cells and it is used by phagocytes
in phagosomes as a weapon to kill