Inhibition of arachidonic acid

The mechanisms by which antitumor-promoters suppress the tumor promotion are not known, but may be due to the following effects (i) inhibition of polyamine metabolism (ii) inhibition of arachidonic acid metabolism (iii) protease inhibition (iv) induction of differentiation (v) inhibition of oncogene expression (vi) inhibition of PKC and (vii) inhibition of oxidative DNA damage [3,6,91]. The polyamine content of cells is correlated to their proliferative, and often, their neoplastic capabilities. A key enzyme in the polyamine biosynthetic pathway, ornithine decarboxylase (ODC), catalyzes the convertion of ornithine to putrescine. Phorbol ester promoters such as TPA cause increased ODC activity and accumulation of polyamines in affected tissues. Diacylglycerol activated PKC, and the potent tumor promoter, TPA, binds to, and activates PKC, in competition with diacylglycerol. PKC stimulation results in phosphorylation of regulatory proteins that affect cell proliferation. Some chemopreventive agents have inhibitory activity towards PKC. Refer to recent review articles for further discussion [3,6,91]. 

B) Inhibition of arachidonic acid metabolism. Most flavonoids tested (flavone, chrysin, phloretin, flavanone, apigenin and kaempferol) inhibited... 

Hall, E.D. and Travis, M.A. (1988) Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006F, Brain Res. 451, 350-352. 

Pharmacological inhibition of arachidonic acid metabolism by aspirin impairs platelet-platelet interactions but does not affect platelet adhesion (figure 3). The antiplatelet effects of aspirin are evident in blood anticoagulated with citrate [61,62] and less obvious in studies with native (non anticoagulated) blood [63]. 

Dehmlow, C., Murawski, N., de Groot, H. Scavenging of reactive oxygen species and inhibition of arachidonic acid metaboUsm by silibinin in human cells. Life Sci. 1996 58 1591-1600... 

Sandrosaponin I was the most active, with an inhibition percentage of around 90% at the highest dose. Without excluding the participation of other possible mechanisms, including non-eicosanoid mediators, our data support the inhibition of arachidonic acid (AA) metabolism as one of the biochemical mechanisms which may contribute to the anti-inflammatory activity of these saikosaponins. 

The inhibition of arachidonic acid metabolism by diarylheptanoids can be attributed to their antioxidant properties. Studies on structure-activity relationships demonstrated that hydroxyl groups were responsible for the antioxidant activity, while an unsubstituted phenyl... 

For the reasons given above, agents that interfere with leukotriene synthesis or actions, are of great interest in relation to limiting inflammatory reactions. The sites amenable to pharmacological manipulation include (I) the upstream inhibition of arachidonic acid production from phospholipids (which is a rate-limiting step see PHOSPHOLIPASE inhibitors) (2) the inactivation of five-... 

Robison T, Sevanian A, Forman H. Inhibition of arachidonic acid release by nordihydroguaiaretic acid and its antioxidant action in rat alveolar macrophages and Chinese hamster lung fibroblasts. Toxicol Appl Pharmacol 1990 105 113-22. 

Penneys NS. Inhibition of arachidonic acid oxidation in vitro by vehicle components Acta Dermatovener 1982 62 59-61. 

Brand-Schieber, E., J.F. Falck, and M. Schwartzman (2000). Selective inhibition of arachidonic acid epoxidation in vivo. J. Physiol. Pharmacol. 51, 655-672. 

Studies conducted in our laboratories examined the effects of such conjoint therapy with antibiotics on eicosanoid levels and survival in septic shock. In the rat faecal peritonitis model, improved survival time was observed with early treatment with steroids. However, this protection appears to be independent of inhibition of arachidonic acid metabolism. Corticosteroid pretreatment effected no more than a 30 and 40% inhibition of plasma levels of iTxB2 and i6-keto-PGFi3( respectively, compared with 100% inhibition with the cyclo-oxygenase inhibitors. Conjoint steroid and NSAID treatment improved survival time compared with each drug employed individually. The combination of steroid, NSAID and gentamicin produced the most significant effect on survival. 

Halushka, P.V., Wise, W.C. and Cook, J.A. (1983). Studies on the beneficial effects of aspirin in endotoxin shock. Relationship to inhibition of arachidonic acid metabolism. Am. ]. Med., 14, 91-96... 

The compound curcumin exhibited significant antiplatelet activity in vitro, causing inhibition of arachidonic acid-, collagen- and ADP-induced platelet aggregation with IC50 values of 13.8, 22.4, and 16.8 pM, respectively (Jantan et al. 2007). Inhibition of arachidonate-induced platelet aggregation was observed in human blood platelets treated with turmeric extract (Srivastava 1989). In a similar study, curcumin... 

Some inhibition of arachidonic acid-induced platelet aggregation in guinea pig and rat plasma was observed after treatment with Oswego tea essential oil (Tognolini et al. 2006). 

In human plasma, the compound eugenol strongly inhibited platelet aggregation induced by platelet-activating factor. A weaker inhibition was observed on platelet aggregation induced by arachidonic acid or collagen (Saeed et al. 1995). Inhibition of arachidonic acid-induced platelet inhibition was also observed in rabbit plasma (Laekeman et al. 1990). 

Ferrandiz, M.L., and Alcaraz, M.J. (1991) Anti-Inflammatory Activity and Inhibition of Arachidonic Acid Metabolism by Flavonoids, Agents Actions 32, 283-288. 

Meier, R.W., Niklaus, G., Dewald, B., Fey, M.F., and Tobler, A. (1995) Inhibition of Arachidonic Acid Pathway Prevents Induction of IL-8 mRNA by Phorbol Ester and Changes the Release of IL-8 from HL 60 Cells Differential Inhibition of Induced Expression of IL-8, TNF-a, IL-a and IL-ip, 7. Cell Physiol. 165,62 70. 

There is evidence that anti-inflamnatory steroids can inhibit prostaglandin biosynthesis by the inhibition of arachidonic acid release fron phospholipid stores (17-19). It was of interest, therefore, to examine the effects of an anti-inflairmatory steroid on PGF-M excretion in man (20). Six healthy male subjects (aged 27-34) were screened for any possible predisposition to the side-effects of antiinflammatory steroids Consecutive 24 hour urines were then collected... 

Inhibition of Arachidonic Acid Metabolism by Radicai Scavengers... 

In summary, we can say that the inhibition of platelet aggregation by EPA does not necessarily require the replacement of endogenous arachidonic acid and the inhibition of arachidonic acid oxygenation. Small amounts of EPA might act in modulating the peroxide tone of the cell. On the other hand, DHA is even more potent than EPA for inhibiting platelet aggregation but the respective mechanisms for such inhibitions appear entirely different. 

The effects of 1,8 cineole on stimulated human monocyte mediator production were studied in vitro and compared to that of budesonide, a corticosteroid agent with anti-in ammatory and immunosuppressive effects (Juergens et al., 1998a). At therapeutic levels, both substances demonstrated a similar inhibition of the in ammatory mediators leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and interleukin ip (IL ip).This was the rst evidence of a steroid-like inhibition of arachidonic acid metabolism and IL ip production by 1,8 cineole. 

Juergens, U. R., Stober, M., Schmidt-Schilling, L., Kleuver, T., Vetter, H. 1998c. Antiin ammatory effects of eucalyptol (1,8-cineole) in bronchial asthma Inhibition of arachidonic acid metabolism in human blood monocytes ex vivo. Eur. J. Med. Res. 3 407-412. 

A recent study showed that some isomers of CLA can alter the synthesis of COX products of arachidonic acid by cultured endothelial cells (Urquhart et al., 2002). Different isomers of CLA may have different effects on arachidonic acid metabolism. A dietary study reported that feeding a mixture of CLA isomers to rats resulted in decreased production of PGE by stimulated bone cultures ex vivo (Li and Watkins, 1998). Whether this effect is due to direct inhibition of arachidonic acid metabolism by CLA or to some other mechanism is not clear at this stage. 

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