Isoprostane
Encyclopedia
The isoprostanes are prostaglandin
-like compounds formed in vivo from the free radical-catalyzed peroxidation
of essential fatty acid
s (primarily arachidonic acid
) without the direct action of cyclooxygenase
(COX) enzyme.
These nonclassical eicosanoids possess potent biological activity as inflammatory
mediators that augment the perception of pain
. These compounds are accurate markers of lipid peroxidation
in both animal and human models of oxidative stress
.
Elevated levels of isoprostanes are suspected of contributing to increased risk of heart attack in patients taking Coxibs. Isoprostanes and their metabolites have also been shown to be elevated in the urine of cigarette smokers, and have been suggested as biomarkers of oxidative stress in smokers.
For example, in addition to the four classes of F2-isoprostanes that can arise from arachidonic acid
, peroxidation of eicosapentaenoic acid
(EPA) is predicted to lead to the generation of six classes of F3 isoprostanes, α-linolenic and γ-linolenic acids to two classes of E1- and F1-isoprostanes, and docosahexaenoic acid
to eight classes of D4-isoprostanes and eight classes of E4-isoprostanes. Each of the classes comprise up to eight racemic isomers, leading to an astounding number of isoprostane molecules!|" - LJ Janssen}}
Prostaglandin
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring....
-like compounds formed in vivo from the free radical-catalyzed peroxidation
Lipid peroxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism...
of essential fatty acid
Essential fatty acid
Essential fatty acids, or EFAs, are fatty acids that humans and other animals must ingest because the body requires them for good health but cannot synthesize them...
s (primarily arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
) without the direct action of cyclooxygenase
Cyclooxygenase
Cyclooxygenase is an enzyme that is responsible for formation of important biological mediators called prostanoids, including prostaglandins, prostacyclin and thromboxane. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain...
(COX) enzyme.
These nonclassical eicosanoids possess potent biological activity as inflammatory
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
mediators that augment the perception of pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
. These compounds are accurate markers of lipid peroxidation
Lipid peroxidation
Lipid peroxidation refers to the oxidative degradation of lipids. It is the process in which free radicals "steal" electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism...
in both animal and human models of oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
.
Elevated levels of isoprostanes are suspected of contributing to increased risk of heart attack in patients taking Coxibs. Isoprostanes and their metabolites have also been shown to be elevated in the urine of cigarette smokers, and have been suggested as biomarkers of oxidative stress in smokers.
Abundance
"Polyunsaturated fatty acids other than arachidonic acid are also vulnerable to reactive oxygen species and produce isoprostanes.For example, in addition to the four classes of F2-isoprostanes that can arise from arachidonic acid
Arachidonic acid
Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...
, peroxidation of eicosapentaenoic acid
Eicosapentaenoic acid
Eicosapentaenoic acid is an omega-3 fatty acid. In physiological literature, it is given the name 20:5. It also has the trivial name timnodonic acid...
(EPA) is predicted to lead to the generation of six classes of F3 isoprostanes, α-linolenic and γ-linolenic acids to two classes of E1- and F1-isoprostanes, and docosahexaenoic acid
Docosahexaenoic acid
Docosahexaenoic acid is an omega-3 fatty acid that is a primary structural component of the human brain and retina. In chemical structure, DHA is a carboxylic acid with a 22-carbon chain and six cis double bonds; the first double bond is located at the third carbon from the omega end...
to eight classes of D4-isoprostanes and eight classes of E4-isoprostanes. Each of the classes comprise up to eight racemic isomers, leading to an astounding number of isoprostane molecules!|" - LJ Janssen}}