F2-dihomo-isoprostanes arise from free radical attack on adrenic acid.

Unlike F4-neuroprostanes (F4-NeuroPs), which are relatively selective in vivo markers of oxidative damage to neuronal membranes, there currently is no method to assess the extent of free radical damage to myelin with relative selectively. The polyunsaturated fatty acid adrenic acid (AdA) is susceptible to free radical attack and, at least in primates, is concentrated in myelin within white matter. Here, we characterized oxidation products of AdA as potential markers of free radical damage to myelin in human brain.

Suppression of murine cerebral F2-isoprostanes and F4-neuroprostanes from excitotoxicity and innate immune response in vivo by alpha- or gamma-tocopherol.

Oxidative damage to brain is a featured shared by several destructive and degenerative diseases and is thought to contribute to disease pathogenesis. Two commonly proposed sources of the increased free radical stress that leads to oxidative damage in several of these diseases are excitotoxicity and activation of innate immunity, both of which are proposed pharmacologic targets. Here we used models of excitotoxicity, intracerebroventricular (ICV) kainate (KA), and innate immune activation, ICV lipopolysaccharide (LPS), to test the effectiveness of peripherally administered alpha-tocopherol (AT) and gamma-tocopherol (GT) as neuroprotectants.

Simultaneous resolution of underivatized regioisomers and stereoisomers of arachidonate epoxides by capillary electrophoresis.

cis-Epoxyeicosatrienoic acids (EETs) and their hydrolysis products (threo-DHETs) have been proposed to be endothelial-dependent hyperpolarizing factors (EDHFs) which upregulate blood flow when tissue perfusion is impaired. Various EET regioisomers and enantiomers are formed from arachidonate by inducible cytochrome P450 epoxygenase isoforms, and tissue EET profiles may vary with diet, time, and disease. Because EET actions and metabolism may be regio- and stereospecific, convenient methods to measure profiles of EET isomers in tissues are needed.

Capillary electrophoresis of cytochrome P-450 epoxygenase metabolites of arachidonic acid. 2. Resolution of stereoisomers.

Each of the four regioisomers of epoxyeicosatrienoic acids (EETs) is a candidate for being an endothelial-dependent hyperpolarizing factor (EDHF). One regioisomer, 14,15-EET, stereospecifically blocks cyclooxygenases from converting arachidonic acid to prostaglandins and stereospecifically binds to cellular receptors. Both stereospecific actions emphasize the need to establish the tissue availability of the 14,15-EET enantiomers.

Capillary electrophoresis of cytochrome P-450 epoxygenase metabolites of arachidonic acid. 1. Resolution of regioisomers.

The essential fatty acid arachidonate is oxidized by cytochrome P-450 epoxygenases to four epoxyeicosatrienoic acids (EETs): 14,15-, 11,12-, 8,9-, and 5,6-EETs. Each of the four EET regioisomers and their hydrolysis products (DHETs) has multiple paracrine and autocrine functions and may also potently dilate blood vessels and activate potassium channels. The present work describes a method to resolve EETs and DHETs by capillary electrophoresis (CE) using trimethyl-beta-cyclodextrin and CH3CN as buffer additives.