Inhibition natural lipid

Staurosporine, a natural product isolated from Streptomyces staurosporeus, is a relatively broad, nonspecific protein kinase antagonist, originally isolated in an effort to define inhibitors of protein kinase C (PKC). 7-OH staurosporine (UCN-01) was defined as a more selective, but not specific, PKC antagonist. UCN-01 inhibits classic lipid and calcium-dependent PKCs a, ft, and y (IC50 = 4-30 nM), Ca2+-independent PKCs and less potently (IC 50 approximately 500 nM), and is without effect on the atypical PKCs, e.g., PKC f (97). 

Kelley, D.S., Taylor, P.C., Nelson, G.J., Schmidt, P.C., Ferretti, A., Erickson, K.L., Yu, R., Chandra, R.K. and Mackey, B.E. (1999) Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men. Lipids. 34 317-324. 

In investigations of the effects of various compounds on the activity of an enzyme, vanadate was clandestinely added to inhibit this enzyme (LPP-i) while the experiments purported to show the inhibitory effects of natural lipid effectors the researcher not only falsified his own data but deliberately added vanadate to experiments conducted by colleagues ... 

VITAMIN E AND PLATELET AGGREGATION a-Tocopherol, a natural antioxidant, inhibits platelet aggregation and release. The effect of vitamin E is dne to a redaction in platelet cyclooxygenase activity and inhibition of lipid peroxide formation. It is believed that snpplementing the diet with vitamin E could play a role in the treatment of thromboembolic disease, especially if it is given in conjnnc-tion with an inhibitor of platelet aggregation. 

The carotenoid activity during oxidation is strongly influenced by the oxygen pressure (PO2) of the experimental conditions. Kiokias and Oreopoulou have shown that certain natural carotenoid mixtures (paprika, bixin and tomato, and palm-oil preparations) inhibited the azo-initiated oxidation of sunflower oil-in-water emulsions (operated rapidly under low pOj) in terms of both primary and secondary oxidation products. However, other studies " concluded that carotenoids not only did not inhibit aerial lipid autoxidation (high PO2) but even exerted a prooxidant character, a phenomenon also observed at high carotenoid concentrations that could be due mainly to a more increased formation of carotene-peroxyl radicals, promoting the propagation of autoxidation. 

Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg formation. In most mammals, glucose is the primary substrate for lipogenesis, but in ruminants it is acetate, the main fuel molecule produced by the diet. Critical diseases of the pathway have not been reported in humans. However, inhibition of lipogenesis occurs in type 1 (insulin-de-pendent) diabetes mellitus, and variations in its activity may affect the nature and extent of obesity. 

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

There are other synthetic and natural thiolic compounds possessing antioxidant activity. One such compound is tetradecylthioacetic acid (TTA), which inhibited the iron-ascorbate-induced microsomal lipid peroxidation [234]. Its Se analog exhibited even a more profound antioxidative effect. 

Vitamin B6 (pyridoxine) and its derivative pyridoxamine are apparently able to inhibit superoxide production, reduce lipid peroxidation and glycosylation in high glucose-exposed erythrocytes [353], It was suggested that the suppression of oxidative stress in erythrocytes may be a new mechanism by which these natural compounds inhibit the development of complication in diabetes mellitus. 

Chelators of iron, which are now widely applied for the treatment of patients with thalassemia and other pathologies associated with iron overload, are the intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI) (Figure 19.23, see also Chapter 31). Desferrioxamine (DFO) belongs to a class of natural compounds called siderophores produced by microorganisms. The antioxidant activity of DFO has been studied and compared with that of synthetic hydroxypyrid-4-nones (LI) and classic antioxidants (vitamin E). It is known that chronic iron overload in humans is associated with hepatocellular damage. Therefore, Morel et al. [370] studied the antioxidant effects of DFO, another siderophore pyoverdin, and hydroxypyrid-4-ones on lipid peroxidation in primary hepatocyte culture. These authors found that the efficacy of chelators to inhibit iron-stimulated lipid peroxidation in hepatocytes decreased in the range of DFO > hydroxypyrid-4-ones > pyoverdin. It seems that other siderophores are also less effective inhibitors of lipid peroxidation than DFO [371],... 

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