Lipid oxidation products inhibition

The oxidation hypothesis of atherosclerosis states that the oxidative modification of LDL (or other lipoproteins) is important and possibly obligatory in the pathogenesis of the atherosclerotic lesion thus, it has been suggested that inhibiting the oxidation of LDL will decrease or prevent atherosclerosis and clinical sequelae. LDL oxidation also has important implications for vascular health function. High concentrations of LDL may inhibit arterial function in terms of the release of nitric oxide from the endothelium and many of these effects are mediated by lipid oxidation products. Furthermore, oxidized LDL inhibits endothelium-dependent nitric oxide-mediated relaxations in isolated rabbit coronary arter-... 

Broussochalcone A (32) Antioxidant activity (inhibition of lipid peroxidation) Inhibition of cyclooxygenase Inhibition of nitric oxide production Inhibition of respiratory burst in neutrophils Platelet aggregation inhibitory activity1 [42] [431 [42] [44] [431... 

To learn about the real effects of antioxidants, it is therefore important to obtain specific chemical information about which products of lipid oxidation are inhibited. Several specific assays are needed to elucidate how lipid oxidation products act in the complex multi-step mechanism of lipid oxidative deterioration of foods. The results of several complementary methods are required to determine lipid oxidation products formed at different stages of the free radical chain. Since antioxidants show different activities toward hydroperoxide formation and decomposition, it is important that more than one method be used to monitor Upid oxidation. 

Methylanaline could be transnitrosated with nitrite and S-nitrosocysteine and also by a simulated protein bound nitrite. In the latter case, an important factor was the local concentration of nitrosothiol groups on the matrix. The effects of S-nitrosocysteine as an inhibitor of lipid oxidation, as a color developer, and as an anticlostridial, have been reported recently in a turkey product (31). The Molar concentration of RSNO equating to 25 ppm nitrite gave similar results for color and inhibition of lipid oxidation but had less anti-clostridial activity. Transnitrosation between RSNO and heme protein was demonstrated. 

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... 

It follows from the above that MPO may catalyze the formation of chlorinated products in media containing chloride ions. Recently, Hazen et al. [172] have shown that the same enzyme catalyzes lipid peroxidation and protein nitration in media containing physiologically relevant levels of nitrite ions. It was found that the interaction of activated monocytes with LDL in the presence of nitrite ions resulted in the nitration of apolipoprotein B-100 tyrosine residues and the generation of lipid peroxidation products 9-hydroxy-10,12-octadecadienoate and 9-hydroxy-10,12-octadecadienoic acid. In this case there might be two mechanisms of MPO catalytic activity. At low rates of nitric oxide flux, the process was inhibited by catalase and MPO inhibitors but not SOD, suggesting the MPO initiation. 

Milk contains trace amounts of SOD which has been isolated and characterized it appears to be identical to the bovine erythrocyte enzyme. SOD inhibits lipid oxidation in model systems. The level of SOD in milk parallels that of XO (but at a lower level), suggesting that SOD may be excreted in milk in an attempt to offset the pro-oxidant effect of XO. However, the level of SOD in milk is probably insufficient to explain observed differences in the oxidative stability of milk. The possibility of using exogenous SOD to retard or inhibit lipid oxidation in dairy products has been considered. 

Therefore, the metabolite interferes with mitochondrial function and decreases the production of ATP and other important cofactors such as NADH and FADH. Therefore, after repeated use of the drug, mitochondrial integrity is reduced and cellular and overall liver fat oxidation is inhibited. Consequently, fat accumulates, seen as microvesicular steatosis. Electron microscopy shows swollen mitochondria and damaged mitochondrial structures. The accumulated lipid may encourage lipid peroxidation and oxidative stress to occur, causing further damage. 

A natural question is "Why has this complex pathway evolved to do something that could have been done much more directly " One possibility is that the presence of too much malonyl-CoA, the product of the P oxidation pathway of propionate metabolism (Fig. 17-3, pathways a and c), would interfere with lipid metabolism. Malonyl-CoA is formed in the cytosol during fatty acid biosynthesis and retards mitochondrial P oxidation by inhibiting carnitine palmitoyltransferase i.46 70a 75 However, a relationship to mitochondrial propionate catabolism is not clear. 

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