Indomethacin inhibitor

Antibiotic Diuretic Antiretroviral Protease inhibitor Indomethacin (Indocin) NSAID... 

On the other hand, hydroquinone (3 pmol/L) prevented the staurosporine-induced apoptosis of HL-60 and the IL-3-dependent murine myeloblastic (32D) cell line it also prevented apoptosis of the 32D cells observed in the absence of IL-3. The myeloperoxidase inhibitor indomethacin opposed the effect of hydroquinone on staurosporine-induced apoptosis of HL-60 cells (Hazel et al., 1995, 1996b). Pretreatment of human leukaemia cells ML-1 with buthionine sulfoximine (100 pmol/L for 24 h), in order to decrease their glutathione content, increased the susceptibility of these cells to hydroquinone-induced inhibition of differentiation caused by phorbol acetate pretreatment with l,2-dithiole-3-thione, which induces reduced glutathione synthesis, prevented the differentiation inhibition of hydroquinone. Treatment of DBA/2 mice with 1,2-dithiole-3-thione, which increased the activity of quinone reductase of bone-marrow stromal cells by 50%, decreased the susceptibility of these cells towards hydroquinone (Trush et al., 1996). 

Stimulation of local prostaglandin production is possibly one protective mechanism as quercetin stimulates the enzyme cyclooxygenase and, in addition, the cyclooxygenase inhibitor, indomethacin, reverses me protective effect of quercetin on ethanol-induced ulceration. The increase in prostaglandin synthesis may explain me increase in the amount of mucus observed and its participation in ulcer prevention. Other possible mechanisms include me following ... 

Remmel RP, Crews BC, Kozak KR, et al. Studies on the metabolism of the novel, selective cyclooxygenase-2 inhibitor indomethacin phenethylamide in rat, mouse, and human liver microsomes Identification of active metabolites. DrugMetab Dispos. 2004 32(1) 113-122. 

The role of xenobiotic metabolism in the cytotoxicity of an ecotoxicant to fish cell lines has been best studied with BaP, but even with this PAH the story is incomplete (Table 3). Two types of cytotoxic responses to BaP have been documented. One has been a transitory decline in metabolism, but not in cell viability, after BaP exposures of 24-48 h. This was observed in the rainbow trout liver cell lines, RTL-W1 and Rl174. Metabolism appeared necessary for this effect as the response was blocked in RTL-W1 and Rl by, respectively, the CYP1A inhibitor, a-naphthoflavone (ANF) and the prostaglandin-H-synthase inhibitor, indomethacin. BaP quinones were thought to be the BaP metabolites responsible for this effect. 

In addition to eliciting a contact hypersensitivity response, benzo[a]pyrene has been shown to suppress this response, to other sensitizers. The effects of dermally applied benzo[a]pyrene (alone or following dermal pretreatment with the prostaglandin synthetase inhibitor, indomethacin) on contact hypersensitivity (cell-mediated immunity), and production of antibodies to dinitrophenol (DNP) (humoral immunity) were studied in male BALB/c mice treated for 6 weeks to 6 months (Andrews et al. 1991a). A group of mice treated with acetone served as controls. Benzo[a]pyrene alone caused a significant reduction (p<0.01) in the contact hypersensitivity response to dinitrofluorobenzene (DNFB) as measured by increases in ear thickness when compared to the vehicle controls. However, indomethacin pretreatment prevented the benzo[a]pyrene-induced contact hypersensitivity response. Benzo[a]pyrene also reduced antibody titres to DNP in treated mice. This suppressive effect on humoral immune function was not restored by pretreatment with indomethacin. These findings led the authors to conclude that the mechanism of... 

Further experiments later showed that the more potent PG synthetase inhibitor, indomethacin, can inhibit aspirin acetylation at 1 flM levels. However, indomethacin binding is reversible by treatment with aspirin at several 1 hour intervals, which resulted in complete acetylation of the enzyme. 

The four lactones, kallolides 82-85, isolated from Pseudopterogorgia hallos (Bielschowsky) by Look et al. [54], are closely related to the cembrolide class of compounds and possess the pseudopterane skeleton (i.e. 62). Among these diterpenoids, the major metabolite kallolide 83, displays the same efficacy as the anti-inflammatory inhibitor, indomethacin (see table 1). 

Figure 4.8 PAF (10 ng) bolus injection causes vasodilation in isolated rat lungs perfused with blood at constant flow. This vasodilation is inhibited by CV3988 (I0 molL ) a PAF receptor antagonist but not by the cyclo-oxygenase inhibitor, indomethacin...

In patients with essential hypertension, indomethacin, given by in intramuscular injection at 1 mgkg increases blood pressure and total peripheral vascular resistance associated with diminution of cardiac output". However, reports that indomethacin, given orally at 75-200 mg day for 4-7 days, increases blood pressure in patients with untreated, uncomplicated, essential hypertension contrasts with reports that it does not . Cyclo-oxygenase inhibitors, indomethacin and ibuprofen, were also without effect on blood pressure in patients with renovascular hypertension . Yet, in two siblings with renin-dependent hypertension and aldosteronism, the administration of indomethacin at 250 mg day for 16 days was found to lower blood pressure and plasma renin activity, despite promoting slight retention of salt and water ... 

Zimmerman, B.G., Ryan, M.J., Corner, S. and Kraft, E. (1973). Effect of prostaglandin synthesis inhibitors indomethacin and eicosa-5,8,ll,14-tetraynoic acid on adrenergic responses in dog cutaneous vasculature. ]. Pharmacol Exp. Ther., 187, 315-323... 

Carter, C.A., Ip, M.M., and Ip, C. (1989) A Comparison of the Effects of the Prostaglandin S3mthesis Inhibitors Indomethacin and Carprofen on 7,12-Dimetbylbenz[a]Antbracene-Induced Mammary Tumorigenesis in Rats Fed Different Amounts of Essential Fatty Acid, Carcinogenesis 10,1369-1374. 

Carter, C. A., MithoUand, R.J., Shea, W., and Ip, MM. (1983) Effect of the Prostaglandin Synthetase Inhibitor Indomethacin on 7,12-Dimethylbenz(fl)Anthracene-Induced Mammary Tumorigenesis in Rats Fed Different Levels of Fat, Cancer Res. 43,3559-3562. 

The phospholipase Aj inhibitor dibromoaceto-phenone, the anti-inflammatory steroid fluocino-lone acetonide or the lipoxygenase inhibitor nordi-hydroguiaretic acid just prior to intraperitoneal injection of 100 ng 12-0-tetradecanoylphorbol-13-acetate into unmanipulated CD-I female mice resulted in a dose-dependent decrease in the number of peritoneal exudate cells producing superoxide anion radical as assessed by the reduction of nitro-blue tetrazolium, while the cycloxygenase inhibitor indomethacin had no effect on the number of formazan-positive peritoneal exudate cells caused by PMA treatment (Czerniecki and Witz 1989). 

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