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Deters M.,Poisons Information Center Erfurt | Hutten H.,Otto Von Guericke University of Magdeburg | Kaever V.,Hannover Medical School
Phytomedicine | Year: 2013

The immunosuppressant sirolimus and curcumin, the main principle of the turmeric spice, have shown antiproliferative effects on many human and not-human cell lines. Whereas the antiproliferative effect of sirolimus is mainly mediated by inhibition of mTOR, curcumin is described to affect many molecular targets which makes it unpredictable to appraise if the effects of these both substances on cell proliferation and especially on immunosuppression are additive or synergistic. To answer this question we investigated the interaction of both these substances on OKT3-induced human peripheral blood mononuclear cell (PBMC) proliferation. OKT3-induced human PBMC proliferation was determined by measuring 3H-thymidine incorporation. Influence of curcumin on interleukin-2 (IL-2) release and IκB-phosphorylation in PBMC was determined by ELISA and western blot, respectively. Curcumin-induced apoptosis and necrosis was analyzed by FACS analysis. Whereas curcumin completely inhibited OKT3-induced PBMC proliferation in a dose-dependent manner with an IC50 of 2.8 μM, sirolimus could reduce PBMC proliferation dose-dependently only to a minimum of 28% at a concentration of 5 ng/ml (IC 50 1.1 ng/ml). When curcumin was combined at concentrations of 1.25-2.5 μM with sirolimus at concentrations from 0.63 to 1.25 ng/ml the effects were synergistic. Combination of curcumin (1.25-2.5 μM) with sirolimus (5 ng/ml) showed additive effects. The effects after combination of curcumin at 5 μM with each sirolimus concentration and sirolimus at 10 ng/ml with each curcumin concentration were presumably antagonistic. We conclude that the immunosuppressive effects of curcumin and sirolimus in low concentrations are synergistic in OKT3-activated PBMC. Whether curcumin and sirolimus have also synergistic antiproliferative effects in tumor cells has to be shown in further experiments including animal models. © 2012 Elsevier GmbH. All rights reserved.

Deters M.,Poisons Information Center Erfurt | Bergmann I.,Poisons Information Center Erfurt | Enden G.,Poisons Information Center Erfurt | Kutz S.,Poisons Information Center Erfurt | And 4 more authors.
European Journal of Internal Medicine | Year: 2011

Background: We investigated the toxicity profile of the three main groups of calcium channel antagonists (CCA) and compared mixed CCA exposures (CCA plus another drug) with mono CCA exposures. Methods: All CCA exposures reported to the PIC Erfurt from 2000 to 2009 were analyzed retrospectively. Results: In total, 727 (230 mono and 497 mixed) CCA exposures were registered. Although CCA exposures increased almost twofold from 56 in 2000 to 108 in 2009 their relative frequency to all exposures remained constant. The five CCAs most frequently involved in exposures were the five most frequently prescribed ones in Germany over the same period. In mono and mixed CCA exposures, none or minor symptoms were most often seen with dihydropyridines (mono: 84.7%; mixed: 68.0%) followed by diltiazem (mono: 71.4%; mixed: 62.5%) and verapamil (mono: 57.1%; mixed: 50.0%). Highest rates of moderate (mono: 8.6%: mixed: 20.2%) and severe symptoms (mono: 18.6%; mixed: 23.7%) were observed after verapamil ingestions. Death most frequently occurred with diltiazem (mono: 28.6%; mixed: 12.5%). Rates of moderate symptoms were higher in mixed (13.3%) than in mono CCA exposures (4.8%). No distinct differences were seen regarding the relative frequency of none or minor symptoms, severe symptoms, and death between mono and mixed CCA exposures. Conclusion: Exposures to verapamil more often resulted in moderate and severe symptoms than with dihydropyridines. Death mainly occurred with diltiazem. Moderate symptoms were more frequent in mixed than in mono CCA exposures. The frequency of CCAs involved in exposure was related to their prescription. © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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