Arachidonic acid metabolism peroxidation

Further evidence for the involvement of vitamin E in arachidonic acid metabolism comes from work by Valentovic, Gairola and Lubawy [146], who showed that vitamin E deficiency in rats increased hepatic lipid peroxidation and decreased aortic PGI2 synthesis. Inhalation of cigarette smoke by the rats increased platelet TXA2 by over 90% and reduced aortic PGI2 by between 26-33%. However, these effects were independent of the presence of vitamin E in the diet. 

Saunders, R.D., Dugan, L.L., Demediuk, P., Means, E.D., Horrocks, L.A. and Anderson, D.K. (1987) Effects of methylprednisolone and the combination of alpha tocopherol and selenium on arachidonic acid metabolism and lipid peroxidation in traumatized spinal cord tissue, J. Neurochem. 49, 24-31. 

Yamaja Setty BN, Jurek E, Ganley C, et al Effects of Hydrogen Peroxide on Vascular Arachidonic Acid Metabolism. Prostag. Leuko. Med 1984 14 205-213. 

Asbestos induces NF-kB and AP-1 transcription-factor activation, possibly through ROS-mediated hpid peroxidation and arachidonic acid metabolism. In macrophages, asbestos caused increased release of arachidonic acid and the formation of prostaglandins E2 and F2a In alveolar macrophages, asbestos induced the releases of arachidonic acid metabolites as early as 1 h post-in vitro exposure. Persistent release of arachidonic acid metabolites at sites of asbestos deposition are implicated in the constitutive activation of NF-kB. ... 

Reactive Oxygen Species, Oxygen-Free Radicals, Lipid Peroxides, and Their Interaction with Arachidonic Acid Metabolism... 

Mediators of both the infiammatoiy and fibrotic responses have been associated with exposure to oxidants. Similarly, mediator release after incubation of cells with silica and asbestos can be the result of oxygen-based free radicals catalyzed by iron associated with the mineral oxide (Fig. 1). The increase in arachidonic acid metabolism after exposures of cells to particles and fibers can result from the eooxidation of arachidonate by metal-catalyzed oxidants. This is a lipid peroxidation that can be mediated by free radical production by the dust (83). In support of an association between metal-catalyzed oxidant generation and arachidonic acid products, the release of LTB4 by alveolar macrophages can increase with the eoneentrations of iron complexed to the surface of silica and asbestos (84). Similarly, the eellular release of eytokines postulated to participate in the infiammatory and fibrotic responses ean be associated with exposures to metal-dependent radicals (see Fig. 1). TNF-a produetion by alveolar macrophages after mineral oxide exposure can be inhibited by both the metal chelator deferoxamine and hydroxyl radical scavengers (74). The release of other cytokines pertinent to silica and asbestos exposure ean also be responsive to oxidative stress (85,86). The release of these pertinent mediators after dust exposures is likely to be controlled by oxidant-sensitive promoters such as nuclear factor (NF)-kB (87). After exposure to silica and asbestos, NF-kB can function as a promoter... 

Peroxyl radicals are the species that propagate autoxidation of the unsaturated fatty acid residues of phospholipids (50). In addition, peroxyl radicals are intermediates in the metabolism of certain drugs such as phenylbutazone (51). Epoxidation of BP-7,8-dihydrodiol has been detected during lipid peroxidation induced in rat liver microsomes by ascorbate or NADPH and during the peroxidatic oxidation of phenylbutazone (52,53). These findings suggest that peroxyl radical-mediated epoxidation of BP-7,8-dihydrodiol is general and may serve as the prototype for similar epoxidations of other olefins in a variety of biochemical systems. In addition, peroxyl radical-dependent epoxidation of BP-7,8-dihydrodiol exhibits the same stereochemistry as the arachidonic acid-stimulated epoxidation by ram seminal vesicle microsomes. This not only provides additional... 

Triterpenes are widely distributed in plants, and in many cases are the principles responsible for their anti-inflammatory effects. Many of these compounds are active in different in vivo experimental models such as hind paw edema induced by carrageenan, serotonin and phospholipase A2 ear edema induced by phorbol and daphnane esters, ethylphenylpropiolate, arachidonic acid and capsaicin adjuvant arthritis and experimental models of allergy. Other effects have been studied in vitro, and some triterpenes are active against inflammatory enzymes like 5-lipoxygenase, elastase and phospholipase A2. Others inhibit histamine, collagenase and interleukin release, lipid peroxidation and free radical-mediated processes, metabolism of endogenous corticoids, and complement and protein-kinase activities. 

Monooxygenase metabolism of essential fatty acids has received comparatively little attention. DiAugustine and Fonts found that in liver microsomes, linoleic acid, linolenic acid and arachidonic acid induced spectral changes of type I, which are associated with metabolism, but the products were not identified [394]. These polyunsaturated fatty acids could be expected to be wl- and w2-hydroxylated like their saturated counterparts and to be transformed into hydroxylated cis,trans conjugated products by chemical peroxidation (autooxidation) as discussed above. Recent studies show that cytochrome P-450 can metabolise polyunsaturated fatty acids to a large extent by epoxidation. The epoxides are rapidly hydrolysed to vicinal diols by microsomal or soluble enzymes. 

---