Inhibitors lipoxygenase-specific, effect

Table III. Effect of a lipoxygenase-specific inhibitor on the occurrence of enzymically- and oxidatively-derived volatiles in fish.

In a study by Salari and colleagues (1984), NDGA proved to be a potent and selective inhibitor of 5-lipoxygenase (ID50 < 3x10-1 M). Specifically, it reduces the active ferric form of lipoxygenase to the inactive ferrous form (Kemal et al., 1987). NDGA is also an indirect inhibitor of phospholipase A2 by virtue of its antioxidant effect, it prevents oxidative modification of cell membrane phospholipids (Robison etal., 1990). 

FPL 55712 was found to inhibit the formation of lipoxygenase (LO) products (ICjQ of 20.6 pM for 5-HETE) but had no effect on synthesis of cyclooxygenase (CO) products in a cell-free homogenate of rat basophilic leukemic (RBL) cells. This finding is significant because other SRSA antagonists may also be specific 5-LO inhibitors and vice versa. Aryl AA analog was shown to inhibit the formation of 5-HETE and LTB from intact... 

Caffeic Acid Phenethyl Ester (CAPE). CAPE, a phenolic compound with antioxidant properties, is an active ingredient derived from honeybee propolis (52). CAPE has antiviral, anti-inflammatory and antiproliferative properties. The compound differentially suppresses the growth of numerous human cancer cells and also inhibits tumor promoter-mediated processes in transformed cells (53,54). In transformed cells, CAPE induces apoptosis and inhibits the expression of the malignant phenotype (55,56). In addition, CAPE treatment attenuates the formation of azoxymethane-induced aberrant crypts and the activities of ornithine decarboxylase (ODC), tyrosin protein kinase, and lipoxygenase activity (57). Although the molecular basis for these multiple chemopreventive effects of CAPE is not clear, recent studies have demonstrated that CAPE is a potent and specific inhibitor of the transcription factor NF-kB (58). CAPE inhibited the activity and expression of COX-2 in the carrageenan air pouch model of inflammation as well as in TPA-treated human oral epithelial cells (59). CAPE was able to reduce neointimal formation by inhibiting NF-kB activation in a model of endothelial injury of rat carotid artery (60). 

A protease inhibitor, L-l-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), specific for chymotrypsin, has been shown to exert a number of effects on platelet processes. This compound also interferes with arachidonic acid metabolism in platelets. The 12-lipoxygenase was inhibited by TPCK, but the main effect was an irreversible inhibition of thromboxane synthetase [157]. 

Specific 15-lipoxygenase inhibitors are not yet available, but several drugs that inhibit 12-lipoxygenase and 5-lipoxygenase activities (e.g., NDGA) exert a similar inhibitory effect on 15-lipoxygenase. 

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