Isoprostane

Isoprostanes are a series of prostaglandin-like compounds formed by the free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. They were first discovered in the early 1990s and have since been recognized as reliable markers of oxidative stress and lipid peroxidation in the human body. Isoprostanes are formed in situ on phospholipids and then released by the action of phospholipase A2, after which they can be metabolized in a manner similar to prostaglandins or excreted in urine.

Biosynthesis and Structure

Isoprostanes are generated through a complex process initiated by the attack of free radicals on the arachidonic acid embedded in cell membrane phospholipids. This process leads to the formation of various isoprostane isomers, depending on the specific sites of free radical attack and subsequent rearrangements. The most studied isoprostanes are the F2-isoprostanes, which are considered the gold standard for assessing oxidative stress in vivo.

Physiological and Pathological Roles

Isoprostanes exert a wide range of biological effects, some of which mimic those of classical prostaglandins, including vasoconstriction, platelet aggregation, and modulation of inflammation. Elevated levels of isoprostanes have been detected in various diseases and conditions associated with oxidative stress, such as cardiovascular diseases, neurodegenerative disorders, and pulmonary diseases. As such, they are not only markers of oxidative stress but may also contribute to the pathophysiology of these conditions.

Measurement and Clinical Significance

The measurement of isoprostanes, particularly 8-iso-PGF2α (an F2-isoprostane), in biological fluids such as plasma and urine, is considered a reliable biomarker of oxidative stress. High-performance liquid chromatography (HPLC) coupled with mass spectrometry (MS) is the most accurate method for quantifying isoprostanes, allowing for the detection of specific isomers and providing insights into the mechanisms of oxidative injury in different diseases.

Research and Therapeutic Implications

Research on isoprostanes has provided valuable insights into the mechanisms of oxidative damage and its role in disease pathogenesis. Understanding the pathways of isoprostane formation and action may lead to the development of novel therapeutic strategies aimed at reducing oxidative stress. Antioxidant therapy, aimed at reducing the formation of isoprostanes, has been explored in various clinical trials with mixed results, highlighting the need for further research in this area.

See Also

• Oxidative stress
• Prostaglandin
• Arachidonic acid
• Lipid peroxidation
• Free radical