Leukotriene B4 production

M. Salami, A. Sala, and C. Galli. Inhibition of leukocyte leukotriene B4 production by an olive oil-derived phenol identified by mass-spectrom- OE047 etry. Thrombosis Res 1997 87(3) ... 

Immunoglobulin level. The effect of sesaminol and sesamin on the ethanol-induced immune indices were examined in rats given a low (10%)-casein diet. Sesaminol decreased splenic leukotriene B4 production, whereas sesamin increased the plasma PGE2 concentration. A significant IgG-elevating effect of these lignans was observed. The concentration of plasma IgE was not influenced . 

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

Alveolar macrophages release a number of inflammatory mediators, including PAF and leukotrienes B4, C4, and D4. Production of neutrophil chemotactic factor and eosinophil chemotactic factor furthers the inflammatory process. 

The cytosolic enzyme leukotriene A4 hydrolase (EC 3.3.2.6), which ster-eoselectively converts leukotriene A4 (LTA4) to leukotriene B4 [56], This enzyme catalyzes the hydrolytic cleavage of the 5,6-epoxide ring in LTA4, but, in contrast to what happens with other EHs, the product is not a vicinal diol but a 5,12-diol. As a zinc metalloenzyme, LTA4 hydrolase does not appear to be related to any other epoxide hydrolase. 

The biological actions of the cysteinyl leukotrienes are mediated via stimulation of CysLTi receptors. Montelukast and zafirlukast are competitive antagonists of these receptors. In contrast, zileuton suppresses synthesis of the leukotrienes by inhibiting 5-lipoxygenase, a key enzyme in the bioconversion of arachidonic acid to the leukotrienes. Zileuton also blocks the production of leukotriene B4, another arachidonic acid metabolite with proinfiammatory activity. The CysLTi-receptor antagonists alter neither the production nor the actions of leukotriene B4. 

Gold alters the morphology and functional capabilities of human macrophages—possibly its major mode of action. As a result, monocyte chemotactic factor-1, interleukin-8, interleukin-IB production, and vascular endothelial growth factor are all inhibited. Intramuscular gold compounds also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivate the first component of complement, and suppress the phagocytic activities of polymorphonuclear leukocytes. Auranofin also inhibits release of prostaglandin E2 and leukotriene B4. 

More than 11,000 Sesquiterpenes have been isolated from natural sources [3]. Feverfew (Tanacetum parthenium (L.) Sch. Bip.,. Compositae) is a common herb utilized for fever, arthritis and migraine. The leaves of feverfew contain large amounts of sesquiterpene lactones. The chloroform extracts of fresh leaves and a commercial leaf product show dose-dependent inhibiting the production of throboxane B2 (TXB2) and leukotriene B4 (LTB4) in rat and human leukocytes. Sesquiterpene lactones isolated from the leaves of feverfew, such as parthenolide and tanaparthin-a-peroxide, demonstrate potent dual inhibitions of COX and LOX pathways with IC50 for COX at 6 17 pg/ml, and for LOX at 12 17 pg/ml, respectively [135],... 

Gossypol has been isolated from the roots, stems, and seeds of the cotton plant and reported as a COX inhibitor based on in vitro assay in neutrophils [165] and an inhibitor of LOX and prostaglandin synthase from rat basophilic leukemia cells [166]. Gossypol showed as a potent inhibitor of leukotrienes B4 and D4 production and also reduced PTF-induced contraction of guinea-pig lung parenchyma [167]. 

In Hoult s report, sixteen natural and synthetic coumarins were evaluated in rat peritoneal exudate leukocytes for the impact on production of throboxane B2 and leukotriene B4. (Table 4.) Four coumarins exhibited... 

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