Isoprostanes

Peroxidation is also catalyzed in vivo by heme compounds and by lipoxygenases found in platelets and leukocytes. Other products of auto-oxidation or enzymic oxidation of physiologic significance include oxysterols (formed from cholesterol) and isoprostanes (prostanoids). 

A major drawback of this study was that we measured lipid peroxidation ex vivo, but not in vivo using the latest and most promising methods such as F2 isoprostanes (Roberts and Morrow, 2000). However, we are planning to do that soon, so hopefully future studies will bring us more detailed information about the effects of phloem on lipid peroxidation. In conclusion, our study showed that lignans are bioavailable from the wood matrix, that long-term consumption of phloem is safe and that ingestion of phloem can inhibit lipid peroxidation in humans. 

ROBERTS L J, MORROW J D (2000) Measurement of F2-isoprostanes as an index of oxidative stress in vivo, Free Radical Biology and Medicine, 28, 505-13. 

VANHARANTA M, VOUTILAINEN S, NURMI T, KAIKKONEN J, ROBERTS L J, MORROW J D, ADLERCREUTZ H, SALONEN J T (2002b) Association between low serum enterolactone and increased plasma F2-isoprostanes, a measure of lipid peroxidation, Atherosclerosis, 160,465-9. 

However, peroxidation can also occur in extracellular lipid transport proteins, such as low-density lipoprotein (LDL), that are protected from oxidation only by antioxidants present in the lipoprotein itself or the exttacellular environment of the artery wall. It appeats that these antioxidants are not always adequate to protect LDL from oxidation in vivo, and extensive lipid peroxidation can occur in the artery wall and contribute to the pathogenesis of atherosclerosis (Palinski et al., 1989 Ester-bauer et al., 1990, 1993 Yla-Herttuala et al., 1990 Salonen et al., 1992). Once initiation occurs the formation of the peroxyl radical results in a chain reaction, which, in effect, greatly amplifies the severity of the initial oxidative insult. In this situation it is likely that the peroxidation reaction can proceed unchecked resulting in the formation of toxic lipid decomposition products such as aldehydes and the F2 isoprostanes (Esterbauer et al., 1991 Morrow et al., 1990). In support of this hypothesis, cytotoxic aldehydes such as 4-... 

Tangirala, RK, Pratico, D, FitzGerald, GA, Chun, S, Tsukamoto, K, Maugeais, C, Usher, DC, Pure, E, and Rader, DJ, 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J Biol Chem 276, 261-266. 

The determination of F2-isoprostanes, oxidation products of arachidonic acid, has been proposed as a more reliable index of oxidative stress in vivo, overcoming many of the methodological problems associated with other markers. The isoprostanes have emerged as a most effective method of quantifying the potential of antioxidants to inhibit lipid peroxidation. However, one drawback of this method is that quantification of F2-iP requires sophisticated techniques, in particular GC/MS and HPLC/MS... 

Fowke JH, Morrow JD, Motley S, Bostick RM and Ness RM. 2006. Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake. Carcinogenesis 27(10) 2096-2102. 

Sanchez-Moreno C, Cano MP, De Ancos B, Plaza L, Olmedilla B, Granado F, Elez-Martinez P, Martin-Belloso O and Martin A. 2004a. Pulsed electric fields-processed orange juice consumption increases plasma vitamin C and decreases F2-isoprostanes in healthy humans. J Nutr Biochem 15(10) 601—... 

Thompson HJ, Heimendinger J, Sedlacek S, Haegele A, Diker A, O Neill C, Meinecke B, Wolfe P, Zhu Z and Jiang W. 2005. 8-Isoprostane F2a excretion is reduced in women by increased vegetable and fruit intake. Am J Clin Nutr 82(4) 768-776. 

As in the case of linear peroxidation products, the initiation step of the formation of isoprostanes is the abstraction of a hydrogen atom from unsaturated acids by a radical of initiator. Initiation is followed by the addition of oxygen to allylic radicals and the cyclization of peroxyl radicals into bicyclic endoperoxide radicals, which form hydroperoxides reacting with hydrogen donors. 

Finally, hydroperoxides are reduced to trihydroxy compounds (Figure 25.6). As seen from Figure 25.6, the oxidation of AA resulted in the formation of four F2-isoprostane regio-isomers, each of which is a mixture of eight racemic diastereomers. It is important that the level of F2-isoprostanes in normal human plasma and urine are one to two orders of magnitude higher than the level of COX-derived prostaglandins. 

FIGURE 25.6 The formation of F2-isoprostane by the oxidation of arachidonic acid. 

In the last decade numerous studies were dedicated to the study of biological role of nonenzymatic free radical oxidation of unsaturated fatty acids into isoprostanes. This task is exclusively difficult due to a huge number of these compounds (maybe many hundreds). Therefore, unfortunately, the study of several isoprostanes is not enough to make final conclusions even about their major functions. F2-isoprostanes were formed in plasma and LDL after the treatment with peroxyl radicals [98], It is interesting that their formation was observed only after endogenous ascorbate and ubiquinone-10 were exhausted, despite the presence of other antioxidants such as urate or a-tocopherol. LDL oxidation was followed by... 

Thus, the formation of isoprostanes is rightly considered as a unique noninvasive method for the estimation of in vivo lipid peroxidation. However, the use of 8-Ao-PGF2a isoprostane (now known as iPF2a-III) as an index of nonenzymatic in vivo peroxidation has some limitations due to the possibility of its formation by COX-1- and COX-2-catalyzed... 

At present, antioxidants are extensively studied as supplements for the treatment diabetic patients. Several clinical trials have been carried out with vitamin E. In 1991, Ceriello et al. [136] showed that supplementation of vitamin E to insulin-requiring diabetic patients reduced protein glycosylation without changing plasma glucose, probably due to the inhibition of the Maillard reaction. Then, Paolisso et al. [137] found that vitamin E decreased glucose level and improved insulin action in noninsulin-dependent diabetic patients. Recently, Jain et al. [138] showed that vitamin E supplementation increased glutathione level and diminished lipid peroxidation and HbAi level in erythrocytes of type 1 diabetic children. Similarly, Skyrme-Jones et al. [139] demonstrated that vitamin E supplementation improved endothelial vasodilator function in type 1 diabetic children supposedly due to the suppression of LDL oxidation. Devaraj et al. [140] used the urinary F2-isoprostane test for the estimate of LDL oxidation in type 2 diabetics. They also found that LDL oxidation decreased after vitamin E supplementation to patients. 

A number of early in vitro studies demonstrated a considerable role of free radicals in liver injury (see, for example, Proceedings of International Meeting on Free Radicals in Liver Injury [341]). Later on, it was shown that chronic inflammation in the liver-induced oxidative DNA damage stimulated chronic active hepatitis and increased the risk of hepatocarcinogenesis [342,343]. Farinati et al. [344] showed that 8-OHdG content increased in circulating leukocytes of patients with chronic hepatitis C virus (HCV) infection. DNA oxidative damage is supposedly an early event of HCV-related hepatitis. The formation of isoprostanes in the liver of carbon tetrachloride-treated rats can be suppressed by the administration of vitamin E [345],... 

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