Docosahexaenoic acid oxidation

Chucair, AJ, Rotstein, NP, Sangiovanni, JP, During, A, Chew, EY, and Politi, LE, 2007. Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress Relation with docosahexaenoic acid. Invest Ophthalmol Vis Sci 48, 5168-5177. 

Mukherjee, P. K., Marcheselli, V. L., Serhan, C. N. and Bazan, N. G. Neuroprotectin Dl a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc. Natl Acad. Sci. U.S.A. 101 8491-8496, 2004. 

For the NO studies that show inhibition of lipid peroxidation, we used HL-60 cells made more oxidizable by adding 32 pM docosahexaenoic acid (22 6q)3 ) to the growth media. When unenriched cells were examined, inhibition of oxidation was qualitatively identical, but the magnitude of the effect was less, and therefore more difficult to measure. The effect of lipid unsaturation will be developed below. 

Mectianism of Action A combination of ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that inhibits acyl coenzyme A l,2-diacylglycerol acyltransferase and increases peroxisomal oxidation in the liver. Therapeutic Effect Reduces the synthesis of triglycerides in the liver. 

Ferdinandusse, S., Denis, S., Mooijer, PA. etal., Identification of the peroxisomal beta-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid, J. Lipid Res., 42, 1987, 2001. 

Ikeda, I., Cha, J. Y., Yanagita, T., Nakatani, N., Oogami, K., Imaizumi, K., and Yazawa, K. 1998. Effects of dietary a-linoleic, eicosapentaenoic and docosahexaenoic acids on hepatic lipogenesis and P-oxidation in rats. Biosci. Biotech. Biochem., 62, 675-680. 

Following peroxidation of n-6 (linoleic, y-linolenic and arachidonic acids) and n-3 (a-linolenic and docosahexaenoic acids) fatty acids, relatively unstable fatty acid hydroperoxides may be converted by consecutive scission, fission, rearrangement and oxidation reactions into more stable carbonyls. These include ... 

Similar studies of lipid peroxidation products have been performed for other substrate lipids. Of particular interest are oxidation produets of docosahexaenoic acid (DHA), which have been termed F4-neuroprostanes (F4-NeuroPs) (Roberts et al, 1998). In contrast to AA, which is evenly distributed in all eell types in all tissues, DHA is highly eoneentrated in neuronal membranes (Salem et al, 1986 Montine et al, 2004). Thus, determination of F4-NeuroPs permits the speeifle quantifleation of oxidative damage to neuronal membranes in vivo (Montine et al, 2004). In faet, to our knowledge, F4-NeuroPs are the only quantitative in vivo marker of oxidative damage that is selective for neurons. 

The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo via a nonenzymatic mechanism involving the free radical-initiated peroxidation of arachidonic acid. This article summarizes our current knowledge of these compounds. Herein, a historical account of their discovery and the mechanism of their formation are described. Methods by which these compounds can be analyzed and quantified are also discussed, and the use of these molecules as biomarkers of in vivo oxidant stress is summarized. In addition to being accurate indices of lipid peroxidation, some isoprostanes possess potent biological activity. This activity will be discussed in detail. Finally, in more recent years, isoprostane-like compounds have been shown to be formed from polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid. These findings will be summarized as well. 

Reactive aldehydes generated from hpid peroxidation are involved in CVD (266). Another example lies with the role of oxidative stress in the pathophysiology of asthma (267). Lipid peroxidation, as determined by plasma iso-prostanes, is related to disease severity in mild asthma. Tumor cell lines are sensitive to PUFA and to associated oxidation products (268). This sensitivity depends on the antioxidant defense mechanism, as well as on culture conditions. Hydroperoxy docosahexaenoic acid is a major metabolite, responsible for the cytotoxicity of DHA. 

Petroni, A., Bertagnolio, B., LaSpada, P., Blasevich, M., Papini, N., Govoni, S., Rimoldi, M. and Galli, C. (1998) The beta-oxidation of arachidonic acid and the synthesis of docosahexaenoic acid are selectively and consistently altered in skin fibroblasts from three Zellweger patients versus X-adrenoleukodystrophy, Alzheimer and control subjects. Neurosci. 250 145-148. 

Mori, T.A., Woodman, R.J., Burke, V., Puddey, I.B., Croft, K.D., and Beilin, LJ. 2003. Effect of eicosapentaenoic acid and docosahexaenoic acid on oxidative stress and inflammatory markers in treated-hypertensive type 2 diabetic subjects. Free Radio. Biol. Med. 35, 772-781. 

An interesting example which capitalizes on the ability of the hydro-phobic cavity of (3-lactoglobulin to carry a hydrophobic molecules and complexation has been recently reported (Zimet and Livney, 2009). It was found that (S-lactoglobulin binds docosahexaenoic acid (DHA) and further that DHA-loaded (S-lactoglobulin can form nanocomplexes ( 100 nm) with low methoxy pectin at a pH colloidal stability and protected DHA against oxidation. 

Khair-El-Din TA, Sicher SC, Vazquez MA, Lu CY. Inhibition of macrophage nitric-oxide production and la-expression by docosahexaenoic acid, a constituent of fetal and neonatal serum. Am J Reprod Immunol 1996 36 1-10. 

Fu Z, Sinclair AJ. Increased alpha-linolenic acid intake increases tissue alpha-linolenic acid content and apparent oxidation with little effect on tissue docosahexaenoic acid in the guinea pig. Lipids 2000 35(4) 395 00. 

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