ABSTRACT
The rhizome of Kaempferia parviflora has been used in traditional Thai medicine. In this study, we identified and compared specific compounds from the hexane extract of K. parviflora with those from other Zingiberaceous plants by using gas chromatography-mass spectrometry. We identified 5,7-dimethoxyflavone (DMF), 5-hydroxy-3,7,3',4'-tetramethoxyflavone (TMF), estimated 3,5,7-trimethoxyflavone, 5-hydroxy-7,4'-dimethoxyflavone, 3,5,7,4'-tetramethoxyflavone, and investigated their anti-inflammatory effects in rat basophilic leukemia (RBL-2H3) cells stimulated with an IgE antigen or a calcium ionophore. We found that DMF and TMF more potently inhibited antigen-induced degranulation than did nobiletin, a well-known anti-inflammatory agent. In addition, compared to RBL-2H3 cells stimulated with a calcium ionophore, those treated with DMF and TMF showed more marked inhibition of the degranulation and the production and mRNA expression of inflammatory mediators. These results suggest that DMF and TMF inhibit an early step in the high-affinity IgE receptor signaling cascade rather than intracellular calcium release and protein kinase C activation.
Subject(s)
Anti-Inflammatory Agents/analysis , Anti-Inflammatory Agents/pharmacology , Plant Extracts/analysis , Plant Extracts/pharmacology , Zingiberaceae/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Degranulation/drug effects , Cell Line, Tumor , Chromatography, Liquid , Flavonoids/pharmacology , Gas Chromatography-Mass Spectrometry , Hexanes/chemistry , Inflammation Mediators/metabolism , Plant Extracts/isolation & purification , RatsABSTRACT
Copper-containing nitrite reductases (CuNiRs), which catalyse the reversible one-electron reduction of nitrite to nitric oxide, are members of a large family of multi-copper enzymes that require an interprotein electron transfer (ET) reaction with redox partner proteins. Here, we show that the naturally fused type of CuNiR tethering a cytochrome c (Cyt c) at the C-terminus folds as a unique trimeric domain-swapped structure and has a self-sufficient electron flow system. The C-terminal Cyt c domain is located at the surface of the type 1 copper (T1Cu) site in the N-terminal CuNiR domain from the adjacent subunit, the heme-to-Cu distance (10.6 Å) of which is comparable to the transient ET complex of normal CuNiR with Cyt c. The structural aspects for the domain-domain interface and the ET kinetics indicate that the Cyt c-CuNiR domain interaction should be highly transient. The further electrochemical analysis of the interprotein ET reaction with a cognate redox partner protein suggested that an electron is directly transferred from the partner to the T1Cu. Structural and mechanistic comparisons of Cyt c-CuNiR with another cupredoxin-tethering CuNiR highlight the behaviours of extra domains on the fusion types of CuNiRs required for ET through proteins.
Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Cytochromes c/chemistry , Cytochromes c/metabolism , Nitrite Reductases/chemistry , Nitrite Reductases/metabolism , Crystallography, X-Ray , Electron Transport , Models, Molecular , Oxidation-Reduction , Protein Interaction Domains and Motifs , Protein Structure, Quaternary , Protein Subunits , Pseudoalteromonas/enzymology , Pulse Radiolysis , Static ElectricityABSTRACT
OBJECTIVE: We report a case of sequential interaction of phenytoin (PHT) and phenobarbital (PB) with fluorouracil (5-FU). CASE REPORT: A male patient aged 60 under treatment with PHT and PB in which serum concentrations of PHT (32.8 µg/ml) and PB (26.7 µg/ml) increased ~ 2-fold after the start of postoperative adjuvant therapy with calcium levofolinate (l-LV) and fluorouracil (5-FU). When the drug interactions of this case evaluated using the Drug Interaction Probability Scale, was assessed as "probable". DISCUSSION: In this case, 5-FU increased PHT, which in turn may have increased the PB concentration, suggesting that when fluoropyrimidine antitumor agents are administered to patients receiving PHT in combination with other drugs, some measures should be taken in consideration of secondary effects of antitumor agents on other drugs that may possibly interact with PHT, including frequent monitoring of blood drug concentration.
Subject(s)
Fluorouracil/pharmacology , Phenobarbital/pharmacokinetics , Phenytoin/pharmacokinetics , Drug Interactions , Humans , Male , Middle Aged , Phenobarbital/adverse effectsABSTRACT
PURPOSE: We reported the first case of phenytoin intoxication due to the concomitant use of phenytoin and TS-1, together with a review of the literature regarding the occurrence of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs such as fluorouracil (5-FU) and tegafur (FT). METHODS: We showed the clinical course of our patient. Reports of phenytoin intoxication due to the concomitant use of phenytoin and fluoropyrimidine antitumor drugs in the English and Japanese language literature up to 2007 were identified by searching Medline and ICHUSHI Web (Japana Centra Revuo Medicina). RESULTS: A patient taking phenytoin and TS-1, a combination preparation of tegafur, gimeracil, and oteracil potassium, experienced lightheadedness and repeated falls associated with an increase in serum phenytoin concentration (32.8 mug/ml) at 1 month after the start of TS-1 treatment. The time lag between initiation of combined treatment and onset of adverse symptoms suggests the presence of an indirect mechanism, rather than direct inhibition of drug-metabolizing enzymes by drugs in TS-1 or their active metabolites. CONCLUSIONS: Plasma phenytoin concentration should be closely monitored in patients receiving TS-1 and phenytoin concomitantly.
