Relevance of arteriovenous concentration differences in pharmacokinetic-pharmacodynamic modeling of midazolam |
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Authors: | B Tuk VM Herben JW Mandema M Danhof |
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Affiliation: | Department of Molecular Pharmacology & Toxicology, University of Southern California, Los Angeles 90033, USA. |
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Abstract: | In macrophages, NF-kappaB can be activated by H2O2 generated by the respiratory burst or added exogenously. The mechanism of H2O2 signaling may involve changes in the cellular redox state or a redox reaction at the plasma membrane; however, the site of H2O2 action cannot be readily ascertained because of its membrane permeability. Ferricyanide, a nonpermeable redox active anion, activated NF-kappaB in the macrophage cell line, J774A.1. In contrast with exogenous H2O2, activation by ferricyanide did not correlate with net oxidation of NAD(P)H or glutathione, suggesting that a transplasma membrane redox reaction itself was the first signaling process in NF-kappaB activation. |
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