Disease relevance of NORDIHYDROGUAIARETIC ACID

• In this report, we evaluated the growth-inhibitory effects of sulindac sulfide, a COX-1 and COX-2 inhibitor; exisulind (sulindac sulfone), a novel proapoptotic agent that does not inhibit COX enzymes; and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor on human lung cancer cell lines [1].
• We conclude that the inhibitors of eicosanoid biosynthesis, NDGA and 5,8,11,14-eicosatetraynoic acid, not only suppress glioblastoma cell proliferation, but also induce increased astrocytic differentiation [2].
• The inhibited glioma cells demonstrated an increase in the number and length of astrocytic processes containing greater numbers of glial filaments, and the NDGA-treated cells also demonstrated extensive lateral pseudopod formation along the processes [2].
• The present procedure, implemented in Fortran 90 and named TGSA-Flex, is deeply detailed and tested over four molecular sets: amino acids, nordihydroguaiaretic acid (NDGA) derivatives, HIV-1 protease inhibitors, and 1-[2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives [3].
• Induction of PCA by Escherichia coli was similarly inhibited (E. coli 10(6) alone = 518 +/- 130; with NDGA 3 microM = 234 +/- 100, n = 2) [4].

Psychiatry related information on NORDIHYDROGUAIARETIC ACID

• In the test sessions, however, animals injected with both drugs showed marked amnesic symptoms, while the groups injected with a low dose of nordihydroguaiaretic acid (NDGA) or with nitro-L-arginine (L-NARG) showed a trend towards amnesia [5].

High impact information on NORDIHYDROGUAIARETIC ACID

• We also investigated the effects of preconditioning on eicosanoid metabolism by using high-performance liquid chromatography and found that 12-hydroxyeicosatetraenoic acid (12-HETE), the stable product of the lipoxygenase pathway, was made during the preconditioning protocol and that 12-HETE accumulation was blocked by NDGA [6].
• In digitonin-permeabilized cells, guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) as well as AlF4- blocked the NDGA-promoted disassembly of the Golgi apparatus, and Gbetagamma (betagamma subunits of heterotrimeric G proteins) reversed this effect [7].
• This peak increased after stimulation with arginine vasopressin or epidermal growth factor and was reduced by preincubation with NDGA [8].
• All these effects were inhibited by the phospholipase A2 inhibitors, quinacrine and nordihydroguaiaretic acid (NDGA), while the lipoxygenase inhibitor, BW755C, had no influence and the cyclooxygenase inhibitor, indomethacin, potentiated the increases in mucosal permeability and N-acetyl-glucosaminidase release [9].
• BN 52021, a specific platelet activating factor antagonist, did not influence the myeloperoxidase activity, but it decreased the formation of malondialdehyde and the increases in mucosal permeability and N-acetyl-beta-glucosaminidase release, although not to the same extent as quinacrine and NDGA [9].

Chemical compound and disease context of NORDIHYDROGUAIARETIC ACID

• Two weeks later, Pseudomonas keratitis recurred in 6 of 7 (85.7%) steroid-treated rabbits, 1 of 8 (12.5%) flurbiprofen-treated rabbits, 1 of 8 (12.5%) NDGA-treated rabbits, and none of 8 vehicle-treated rabbits [10].
• Since NDGA substantially alleviated brain edema, the results suggest that the metabolites of arachidonic acid resulting from the lipoxygenase pathway may contribute to the pathogenesis of cerebral edema [11].

Biological context of NORDIHYDROGUAIARETIC ACID

• Down regulation of protein kinase C (PKC) by pretreatment for 24 hours with 500 nm PMA prevents induction by subsequent stimulation with either PMA or NGA [12].
• BFA and NDGA induced a rapid and transient increase in tau phosphorylation in a site-specific manner on immunoblots [13].
• We have examined the effects of three structurally distinct antioxidants (N-acetylcysteine [NAC], Trolox C [a water-soluble vitamin E derivative], and nordihydroguaiaretic acid [NGA]) on the expression of the c-fos gene over a 2-hour period [12].
• Neither inhibiting the cyclooxygenase pathway with indomethacin, nor the lipoxygenase pathway with nordihydroguaiaretic acid (NDGA) had any effect on the AA observed cytoprotection [14].
• In contrast, treatment of cells with nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, blocked in a concentration-dependent manner (IC50 = 10 microM) IL-1 stimulation of NGF secretion [15].

Anatomical context of NORDIHYDROGUAIARETIC ACID

• Both BW755C and NDGA inhibited NK and LAK cell function at a variety of concentrations [16].
• NDGA inhibition of leukotriene release in freshly isolated rabbit tracheal epithelial cells was assayed by a 3H peptidyl-leukotriene radioimmunoassay [17].
• Indomethacin produced a 63-100% decrease in [3H]AFB1-DNA binding in macrophages from five of seven patients, while NDGA inhibited [3H]AFB1-DNA adduct formation by 19, 40 and 56% in macrophages from three of seven patients [18].
• They indicate that endotoxin and NDGA act synergistically to provoke renal damage in the germ free NDGA-fed rat and suggest that leukocytes are involved in the process [19].
• NDGA effectively inhibited neutrophil function, except for chemotaxis [20].

Associations of NORDIHYDROGUAIARETIC ACID with other chemical compounds

• All four reducing equivalents from the two catechol groups in NDGA can be utilized in the reduction of Eox, leading to the consumption of 4 mol of LOOH/mol of NDGA initially present [21].
• 3. Inversely, treatment of phenylephrine (10 microM)-stimulated VSMCs with NDGA induced DNA fragmentation in a dose-dependent fashion [22].
• In the same system, nordihydroguaiaretic acid (NDGA), AA-861 and L-655,240 showed IC50 values of 250-510, 110-420 nM and 1.7-3.9 microM, respectively [23].
• Indomethacin-resistant relaxations were further reduced by the lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-cyanocinnamate (CDC; 1 muM), nordihydroguaiaretic acid (NDGA; 1 microM), and ebselen (1 microM) [24].
• 2. Addition of indomethacin (5 microM) or BW 755C (10 or 100 microM), but not nordihydroguaiaretic acid (NDGA, 50 microM) or FPL 55712 (10 microM), to the perfusion medium led to a significant inhibition of the increases in PIP and PPP, TxB2 release and oedema formation evoked by intra-arterial injection of 400 pmol ET-1 [25].

Gene context of NORDIHYDROGUAIARETIC ACID

• To rule out the possibility that NDGA will induce apoptosis because of the effects on proteins other than AP-1, we investigated the effect of another AP-1 inhibitor, SP600125, which is specific to Jun-N-terminal kinase [26].
• Further evaluation of the apoptotic process revealed that NDGA and BFA induced a rapid dephosphorylation of BAD and decrease expression of Bcl-2 [27].
• Pretreatment for 15 min with the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 50 microM), but not the cyclooxygenase inhibitor indomethacin (10 microM) or the epoxygenase inhibitor SKF525A (100 microM) inhibited the sustained response to CRF by 48% and the initial spike response to AVP by 38% [28].
• Our results indicate that treatment of cells with NDGA enhances c-myc, p53, and bax protein levels [26].
• In addition, volume regulation was inhibited by the lipoxygenase pathway antagonist nordihydroguaiaretic acid (NDGA, 10 microM), the 5 lipoxygenase antagonists AA-861 (5 microM) and curcumin (20 microM), and by the 5-lipoxygenase activating protein inhibitor L-655,298 (5 microM) [29].

Analytical, diagnostic and therapeutic context of NORDIHYDROGUAIARETIC ACID

• 4. The cyclo-oxygenase inhibitor, indomethacin, the phospholipase A2 inhibitor, mepacrine and the lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), failed to inhibit methacholine-induced relaxation of rat aorta in the co-axial bioassay [30].
• The action of indomethacin, a cyclooxygenase inhibitor, and nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, on oxidative products formed by immune mononuclear cells was studied by flow cytometry [31].
• In an attempt to identify a set of 12/15-LOX-regulated genes, the cDNA subtraction technique, followed by Northern blotting, was performed to screen particular clones, the expression of which was suppressed by the LOX inhibitor nordihydroguaiaretic acid (NDGA) [32].

References