F(2)-isoprostanes: sensitive biomarkers of oxidative stress in vitro and in vivo: a gas chromatography-mass spectrometric approach.

A gas chromatography-mass spectrometric method was developed that allowed the accurate, highly sensitive and specific quantification of F(2)-isoprostanes (F(2)-IsoPs) in different tissues and body fluids. Measurement of F(2)-IsoPs in isolated rat brain mitochondria, HaCaT keratinocytes, human plasma, and microdialysates of human skin has established the occurrence of oxidative stress in a variety of model systems and disease states. F(2)-IsoPs correlated with other markers of lipid peroxidation (e.g., TBARS, HETEs) in experimental models of oxidative stress. F(2)-IsoPs were elevated about 100-fold after iron/ascorbate-induced oxidative stress and 2- to 4-fold after pentylenetetrazol (PTZ)-induced seizures, in hemodialysis patients with end stage renal disease, in psoriasis patients, in HaCaT keratinocytes, and in microdialysates of human skin following UVB irradiation.Both human and experimental studies have indicated associations of F(2)-IsoPs and inflammatory conditions. Anti-inflammatory drugs such as diclofenac did not only suppress the prostaglandin but also the F(2)-IsoP pathway.Microdialysis allows the "near-in vivo" measurement of prostanoid mediators, released in the interstitial space of the dermis under inflammatory conditions.