Isoprostanes are prostaglandin-like compounds that are produced by
free radical mediated peroxidation of lipoproteins.  Levels of 15-
isoprostane F2t (also known as 8-epi-PGF2a or 8-iso-PGF2a) in urine
are useful for the non-invasive assessment of oxidant stress in vivo.
15-isoprostane F2t can be detected in urine samples using the ELISA
Bio Assay technology. 15-isoprostane F2t has also been shown to be a
potent vasoconstrictor in rat kidneys and rabbit lungs, and plays a
causative role in atherogenesis. Elevated isoprostane levels are
associated with hepatorenal syndrome, rheumatoid arthritis,
atherosclerosis, and carcinogenesis.

Oxidative stress is caused by an imbalance between the production of
reactive oxygen species (ROS) and a biological system's ability to
readily detoxify reactive intermediates or easily repair the resulting
damage. Disturbances in the normal redox state of cells can cause
toxic effects through the production of peroxides and free radicals
that damage all components of the cell, including proteins, lipids and
DNA.

In humans, oxidative stress is involved in many diseases, such as,
atherosclerosis, Parkinson’s disease, Myocardial Infarction,
Alzheimer’s disease and Chronic Fatigue syndrome. Oxidative stress is
thought to be linked to certain cardiovascular diseases because
oxidation of LDL in the vascular endothelium is a precursor to plaque
formation.

Short-term oxidative stress may be beneficial in that ROS can trigger
apoptosis and remove damaged cells from an organism. Reactive oxygen
species can also be beneficial in the prevention of aging, they are
used by the immune system as a way to attack and kill pathogens and
ROS are also used in cell signaling processes (redox signaling).

One source of reactive oxygen under normal conditions in humans is the
leakage of activated oxygen from mitochondria during oxidative
phosphorylation. Other enzymes capable of producing superoxide are
xanthine oxidase, NADPH oxidases and Cytochromes P450. Hydrogen
peroxide is produced by a wide variety of enzymes including several
oxidases. Disturbances in the normal redox state of cells can cause
toxic effects through the production of peroxides and free radicals
that damage all components of the cell, including DNA, lipids and
proteins.

Selected Oxidative Damage Biomarkers:

1. DNA damage
8-OHdG:
In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an
oxidized nucleoside of DNA, is the most frequently detected and
studied DNA breakdown product (1). Upon DNA repair, 8-OHdG is excreted
in the urine. Several studies have indicated that urinary 8-OHdG is
not only a biomarker of generalized, cellular oxidative stress but
might also be a risk factor for cancer, atherosclerosis and diabetes
(2-4).

8-OHdG is typically measured in both urine and serum/plasma samples. 8-
OHdG is a hydroxyl radical-damaged guanine nucleotide that has been
excised from DNA by endonuclease repair enzymes. Since repair is known
to normally occur quickly and efficiently, the amount of excised DNA
adducts in urine directly reflects the amount of damage within the
entire body.

2. Lipid Damage
8-epi-PGF2a (F2-Isoprostane):
Lipid peroxidation refers to the oxidative degradation of lipids. It
is the process whereby free radicals take up electrons from the lipids
in cell membranes, resulting in cell damage. It most often affects
polyunsaturated fatty acids, because they contain multiple double
bonds that contain methylene-CH2- groups that possess especially
reactive hydrogen groups.

8-epi-PGF2a (F2-Isoprostane) is the free Radical catalyzed non-
enzymatic oxidation product of arachidonic acid (5). 
Peroxidation of
arachidonic acid occurs in cellular membranes and lipoproteins (i.e.
LDL). The damaged lipid peroxide is excised from the cell wall into
the serum and then excreted in urine. Unlike the reactive aldehydes,
once isoprostanes are formed they are chemically stable and can be
accurately measured in urine.

3. Protein Damage
Nitrotyrosine:
Nitrotyrosine is formed in tissue or blood proteins after exposure to
nitrosating and/or nitrating agents. Reactive nitrogen species such as
peroxynitrite can nitrate specific amino acids, whether free or
protein bound, and nitrotyrosine is believed to be one marker of this
reaction (6,7). Nitrotyrosine has been widely studied and has been
associated as a biomarker for several inflammatory disorders, such as
Alzheimer’s disease, ALS, asthma, atherosclerosis, cardiovascular
disease, COPD, coronary artery disease, Crohn’s, cystic fibrosis,
diabetes, hypercholesterolemia, lung cancer, lung injury, MS,
myocardial inflammation, osteoarthritis and rheumatoid arthritis.

References:
1. Kim H.W., Murakami A., Williams M.V., and Ohigashi H. (2003)
Carcinogenesis 24: 235-241.
2. Kowluru R.A., Atasi L., and Ho Y.S. (2006) Invest. Ophthalmol. Vis.
Sci. 47: 1594-1599.
3. Bowers R. et al. (2004) Am. J. Respir. Crit. Care Med. 169:
764-769.
4. Cui J., Holmes E.H., Greene T.G., and Liu P.K. (2000) Faseb J. 14:
955-967.
5. Morrow, J.D. et al., (1990) PNAS 87; 9383-9387.
6. Beckman, et al (1993) Nature 364, 584.
7. Ayata, et al (1997) J. Neurosci. 17, 6908-6917.

posted by Bolaleman
http://healthylossdiet.blogspot.com/